Academic literature on the topic 'Genetic dyslipidaemia'
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Journal articles on the topic "Genetic dyslipidaemia"
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Austin, Melissa A. "Genetic Epidemiology of Dyslipidaemia and Atherosclerosis." Annals of Medicine 28, no. 5 (January 1996): 459–63. http://dx.doi.org/10.3109/07853899608999108.
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Berberich, Amanda J., and Robert A. Hegele. "The role of genetic testing in dyslipidaemia." Pathology 51, no. 2 (February 2019): 184–92. http://dx.doi.org/10.1016/j.pathol.2018.10.014.
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Marais, A. David. "Dietary lipid modification for mild and severe dyslipidaemias." Proceedings of the Nutrition Society 72, no. 3 (May 17, 2013): 337–41. http://dx.doi.org/10.1017/s0029665113001298.
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The aim of this review is to place a historical perspective on linking dyslipidaemia with atherosclerosis and emphasises previous knowledge about the impact on the lipoprotein profile and health in persons with mild dyslipidaemia and in those with defined genetic disorders. CVD is becoming the leading cause of death and disability in developed and developing countries and is strongly related to lifestyle factors that influence plasma lipoprotein concentrations. It is established that risk of complications from atherosclerosis increases with increasing LDL and decreasing HDL and that there is potentiation of risk when these and other risk factors co-exist. High-fat diets used for losing body mass may increase risk through dyslipidaemia. Pharmaceutical modulation of the lipoproteins has lowered risk powerfully but residual risk persists, possibly relating to existing disease as well as progression relating in many instances to dietary lipids. The impact of various dietary lipids is reviewed as they relate to the conventional lipoprotein profile in persons who do not have significant metabolic defects, as well as the impact on inherited metabolic disease such as familial hypercholesterolaemia, hypertriglyceridaemia and phytosterolaemia. For most persons with dyslipidaemias a significant benefit will be seen on the lipid profile by adopting a low saturated fat diet with less cholesterol intake.
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Chekanova, Valeriya, Nazanin Abolhassani, Julien Vaucher, and Pedro Marques-Vidal. "Association of clinical and genetic risk factors with management of dyslipidaemia: analysis of repeated cross-sectional studies in the general population of Lausanne, Switzerland." BMJ Open 13, no. 2 (February 2023): e065409. http://dx.doi.org/10.1136/bmjopen-2022-065409.
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ObjectivesTo assess the importance of clinical and genetic factors in management of dyslipidaemia in the general population.DesignRepeated cross-sectional studies (2003–2006; 2009–2012 and 2014–2017) from a population-based cohort.SettingSingle centre in Lausanne, Switzerland.Participants617 (42.6% women, mean±SD: 61.6±8.5 years), 844 (48.5% women, 64.5±8.8 years) and 798 (50.3% women, 68.1±9.2) participants of the baseline, first and second follow-ups receiving any type of lipid-lowering drug. Participants were excluded if they had missing information regarding lipid levels, covariates or genetic data.Primary and secondary outcome measuresManagement of dyslipidaemia was assessed according to European or Swiss guidelines. Genetic risk scores (GRSs) for lipid levels were computed based on the existing literature.ResultsPrevalence of adequately controlled dyslipidaemia was 52%, 45% and 46% at baseline, first and second follow-ups, respectively. On multivariable analysis, when compared with intermediate or low-risk individuals, participants at very high cardiovascular risk had an OR for dyslipidaemia control of 0.11 (95% CI: 0.06 to 0.18), 0.12 (0.08 to 0.19) and 0.38 (0.25 to 0.59) at baseline, first and second follow-ups, respectively. Use of newer generation or higher potency statins was associated with better control: OR of 1.90 (1.18 to 3.05) and 3.62 (1.65 to 7.92) for second and third generations compared with first in the first follow-up, with the corresponding values in the second follow-up being 1.90 (1.08 to 3.36) and 2.18 (1.05 to 4.51). No differences in GRSs were found between controlled and inadequately controlled subjects. Similar findings were obtained using Swiss guidelines.ConclusionManagement of dyslipidaemia is suboptimal in Switzerland. The effectiveness of high potency statins is hampered by low posology. The use of GRSs in the management of dyslipidaemia is not recommended.
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Tokgozoglu, Lale, Carl Orringer, Henry N. Ginsberg, and Alberico L. Catapano. "The year in cardiovascular medicine 2021: dyslipidaemia." European Heart Journal 43, no. 8 (February 3, 2022): 807–17. http://dx.doi.org/10.1093/eurheartj/ehab875.
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Abstract The past year was an exciting time for clinical lipidology when we learnt more about existing therapies as well as therapies targeting novel pathways discovered through genetic studies. LDL cholesterol remained the main target and a variety of drugs to lower LDL cholesterol through different mechanisms were explored. Emerging evidence on the atherogenity of triglyceride-rich lipoproteins led to renewed interest in lowering them with new treatments. Lp(a) was back in focus with evidence on causality and new targeted therapeutics which dramatically lower Lp(a) levels. We will be able to personalise lipid lowering therapy further with this enriched armamentarium once we have the results of the cardiovascular outcome studies with some of these new agents.
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Klug, E. Q., F. J. Raal, A. D. Marais, C. M. Smuts, C. Shamroth, D. Jankelow, D. J. Blom, and D. A. Webb. "Klug E, Raal FJ, Marais AD, et al. South African Dyslipidaemia Guideline Consensus Statement 2018 Update: A joint statement from the South African Heart Association (SA Heart) and the Lipid and Atherosclerosis Society of Southern Africa (LASSA). S Afr Med J 2018;108(11b):973-1000." South African Medical Journal 108, no. 11 (November 1, 2018): 973–1000. http://dx.doi.org/10.7196/samj.2018.v108i11.13383.
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South Africa (SA) is home to a heterogeneous population with a wide range of cardiovascular risk factors. Cholesterol reduction in combination with aggressive management of modifiable risk factors, including nutrition, physical activity, blood pressure and smoking, can help to reduce and prevent morbidity and mortality in individuals who are at increased risk of cardiovascular events. This updated consensus guide to management of dyslipidaemia in SA is based on the updated European Society of Cardiology and European Atherosclerosis Society dyslipidaemia guidelines published in 2016. For individuals who are not considered to be at high or very high cardiovascular risk, the decision whether to treat and which interventional strategy to use is based on a cardiovascular risk score calculated using total cholesterol, high-density lipoprotein cholesterol (HDL-C), gender, age and smoking status. The cardiovascular risk score refers to the 10-year risk of any cardiovascular event and includes 4 categories of risk (low, moderate, high and very high). People with established cardiovascular disease, diabetes mellitus, chronic kidney disease and genetic or severe dyslipidaemias are considered to already be at high or very high risk and do not require risk scoring. Therapeutic lifestyle change is the mainstay of management for all patients. The need for and intensity of drug therapy is determined according to baseline low-density lipoprotein (LDL-C) levels and the target LDL-C concentration appropriate to the individual. LDL-C treatment targets are based on pre-treatment risk and are as follows: <3 mmol/L in low- and moderate risk cases; <2.5 mmol/L and a reduction of at least 50% if the baseline concentration is 2.5 - 5.2 mmol/L in high-risk cases; and <1.8 mmol/L and a reduction of at least 50% if the baseline concentration is 1.8 - 3.5 mmol/L in very high-risk cases. A statin is usually recommended first-line; the specific agent is based on the required degree of cholesterol reduction, comorbidities and co-prescribed medication. Special attention should be paid to children with a family history of genetic or severe dyslipidaemia, who should be screened for dyslipidaemia from 8 years of age. In SA, HIV infection is not considered to be a significant cardiovascular risk factor and treatment recommendations for HIV-positive individuals are the same as for the general population, with careful choice of pharmacotherapy to avoid potential adverse drug-drug interactions. The benefit of statins in individuals older than 70 years is uncertain and clinical judgement should be used to guide treatment decisions and to avoid side-effects and overmedication in this group.
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Nicholls, Stephen J. "Management of Severe Dyslipidaemia: Role of PCSK9 Inhibitors." European Cardiology Review 13, no. 1 (2018): 9. http://dx.doi.org/10.15420/ecr.2018.3.2.
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in regulation of LDL receptors on the hepatocyte surface and therefore is essential for effective removal of LDL particles from circulation. Genetic and biochemical studies have established that altered PCSK9 functionality influences both LDL cholesterol levels and cardiovascular risk. This has prompted development of inhibitory strategies targeting PCSK9. Study of monoclonal PCSK9 antibodies has progressed to the clinic, where they have been found to lower LDL cholesterol levels and reduce cardiovascular event rates in large, clinical outcome trials. The use of PCSK9 inhibitors in the setting of dyslipidaemia is reviewed.
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E. Toms, Tracey, Deborah P. Symmons, and George D. Kitas. "Dyslipidaemia in Rheumatoid Arthritis: The Role of Inflammation, Drugs, Lifestyle and Genetic Factors." Current Vascular Pharmacology 8, no. 3 (May 1, 2010): 301–26. http://dx.doi.org/10.2174/157016110791112269.
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Toms, Tracey E. "Dyslipidaemia in Rheumatoid Arthritis: The Role of Inflammation, Drugs, Lifestyle and Genetic Factors." Current Vascular Pharmacology 999, no. 999 (December 15, 2009): 1–13. http://dx.doi.org/10.2174/1570209197581151611.
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Slanovic-Kuzmanović, Zorana, Ivan Kos, and Ana-Marija Domijan. "Endocrine, Lifestyle, and Genetic Factors in the Development of Metabolic Syndrome." Archives of Industrial Hygiene and Toxicology 64, no. 4 (December 1, 2013): 581–91. http://dx.doi.org/10.2478/10004-1254-64-2013-2327.
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Abstract Metabolic syndrome (MetS) is a chronic, multi-component disease characterised by central obesity, hyperglycaemia, dyslipidaemia, and hypertension. Since MetS leads to type 2 diabetes, cardiovascular disease, development of certain cancers, and eventually to premature death, it is not surprising that it draws the attention of scientists around the world. The aetiopathology of MetS is complex and still not fully understood. This review focuses on the role of endocrine factors such as cortisol and insulin in the development of MetS. It also takes a look at some of the contributing lifestyle and genetic factors as well as at the current knowledge about its treatment.
Dissertations / Theses on the topic "Genetic dyslipidaemia"
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Zhang, Qiuping. "Genetic variants of lipid transport genes, dyslipidaemia and coronary heart disease." Thesis, Queen Mary, University of London, 1997. http://qmro.qmul.ac.uk/xmlui/handle/123456789/1642.
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Coronary heart disease (CHD) is one of the most common causes of death in Western Countries. Genetic factors playa major role in the aetiology of CHD, however, the primary defects responsible for the disease have not been identified in most cases. With the application of recombinant DNA technology, it is possible to analyse the putative aetiological role of candidate genes. The role of the Lipoprotein Lipase (LPL) gene and the Apolipoprotein AI-CIII-AIV gene cluster were examined in German and Chinese controls, dyslipidaemics and arteriopaths (coronary artery disease and/or peripheral artery disease). Analyses of four allelic distributions (HindIlI-RFLP, Ser447_Ter, Asp9-Asn and Asn291_Ser mutations) of the LPL gene in German and Chinese populations with or without arterial disease did not show any significant frequency differences. In the German group, plasma triglycerides and VLDL-triglycerides were lower in subjects possessing the Ser447_Ter mutation (p=0.06 and < 0.05 respectively), this mutation was also significantly less frequent in the highest tertiles for triglycerides (p<0.02) and VLDL(P<0.04). The Ser447_Ter variant was found at lower frequencies in the Chinese lipaemic subjects. In addition, two disease related genetic variants (Asp9-Asn and Asn291 _Ser) in Europeans were not found in the Chinese group (P<0.03). Analyses of four genotypic distributions (the ApoAI PstI, MspI, XmnI RFLPs and the ApoCIII G3175_C variant) of the ApoAI-CIII-AIV gene cluster in German and Chinese populations with or without arterial disease did not show any significant differences. However, significant associations between high triglyceride, VLDL, TGIHDL ratio and the PstI RFLP at the ApoAI gene were shown in the German group (p=O.OOl, p<0.02 and p<0.04). In the Chinese group, the rare alleles of the Apo CIII G3175 -C variant and the Apo AI MspI polymorphic variant were both found more frequently in the upper tertile distributions for apo CIII levels and plasma triglyceride/HDL ratios (p<0.05 and p<0.04 respectively). The frequencies of two disease related RFLPs of the ApoAI gene (detected Pane 2 b with Mspl and Xmnl) and the ApoC1I1 G3175 -C variant were significantly different (p<0.0006, p<0.004 and p<0.003 respectively) between Chinese and German control groups. Out of eighteen French patients with diabetes m., obesity and severe hypertriglyceridaemia, eight subjects were found to possess mutations at the LPL gene locus by direct DNA sequencing. Three of these: Argl92_Ter (C829_ T); Phe351 _Leu (C1308_ G) and Thr361 -Thr (C1338 _ A) had not previously been described. Thr361_ Thr appears to be a common population polymorphism whose allele frequency in normolipidaemic diabetics was found to be 0.120 (162 chromosomes studied). The others are all rare at frequencies of <0.01 and may contribute to the phenotype by impairi~g clearance of plasma triglycerides. In eleven of the most lipaemic Chinese subjects, Thr361_Thr (C1338_A) was observed, additionally, the previously published mutations, Ala261_ Thr and Ser447 -Ter, were also noticed. Finally, a Finnish kindred, with premature coronary heart disease and decreased HDL cholesterol levels, was identified having an ApoAI variant (Lys107 ~~) by Single-Strand Conformation Polymorphisms (SSCP) and direct DNA sequencing. This variant was caused by a 3 bp deletion of nucleotides 1396 through 1398 in exon 4 of the ApoAI gene. Ten family members were heterozygous for this mutation. Mean serum apoAI and apoAII levels in heterozygotes were reduced by 18% and 220/0, and cholesteryl ester transfer protein activity (CETP) was reduced by 25% compared with unaffected family members (both p<0.05) respectively, while the plasma lecithin:cholesterol acyltransferase (LCAT) activity did not show any difference between heterozygotes and unaffected family members. The ability of the isolated apoAI variant to serve as a co-factor for LCAT in vitro did not differ from that of normal apoAI.
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Tanyanyiwa, Donald Moshen. "Type 2 diabetes mellitus and dyslipidaemia: effects of genetic variation in African populations." Doctoral thesis, Faculty of Health Sciences, 2018. http://hdl.handle.net/11427/30132.
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Background: Low-density lipoproteins (LDL) have been associated with damage to the
cardiovascular system in patients with type 2 diabetes mellitus (T2DM). These patients are
two (2X) to four (4X) times more likely to develop cardiovascular diseases (CVD) compared
to non-diabetic patients due to dysfunctional lipoprotein metabolism. Normal lipid
metabolism involves interconversion and transfer of molecules regulated by several enzymes
such as Apolipoprotein E (ApoE) and proprotein convertase subtilisin/kexin type 9 (PCSK9).
ApoE and PCSK9 are involved in clearance of lipoproteins and therefore, influence lipid
profiles. Association between ApoE and T2DM in cardiovascular diseases have been widely
reported. PCSK9 on the other hand is emerging as an important player in lipid metabolism
but its effects in diabetes are not known. Studies on both ApoE and PCSK9 in African
populations are in its infancy. Each year, CVD kills more people than any other cause of
death. Many CVDs can be traced back to pathological process of atherosclerosis, in which
fatty material collects along walls of arteries, limiting flexibility and obstructing blood flow.
T2DM alone has been classified as a major factor for development of CVD and one of its
complications is the development of dyslipidaemia. Unlike PCSK9, genetic polymorphisms
in ApoE have been well characterised as important dyslipidaemia genetic markers associated
with coronary artery disease. The association between ApoE and PCSK9 gene
polymorphisms with dyslipidaemia in T2DM was evaluated. Diabetic dyslipidaemia presents
as a triad of high triglycerides, high LDL and low high-density lipoprotein (HDL).
Aims and Objectives: This study aimed to evaluate the role of genetic variation in genes
coding for ApoE2 and PCSK9 on dyslipidaemia in South African diabetic patients. Main
objectives’ included recruitment of participants, genetic characterisation of ApoE and PCSK9
and determination of the lipid profiles for the recruited participants.
Methods: Two hundred and forty-four (n=244) participants were recruited from the
Baragwaneth diabetic clinic, using a retrospective approach. The participants comprised of
two groups, (i) dyslipidaemic, and (ii) non-dyslipidaemic (controls). The dyslipidaemic group
was further divided into three groups; i) those with high cholesterol only, ii) those with high
triglycerides only and iii) those with both high cholesterol and triglycerides which is referred
to as the mixed group. Clinical and demographic parameters were retrieved from hospital
records with the consent of the participants. Ethical clearance was obtained from the University of Cape Town and University of Witwatersrand. Genetic characterisation of ApoE
was carried out using polymerase chain reaction (PCR) coupled to restriction fragment length
polymorphism (RFLP) and confirmed through sequencing while characterisation for PCSK9
was carried out through Sanger sequencing.
Results: Of the 244 participants, 165 were dyslipidaemic while 79 were not dyslipidaemic.
The 165 dyslipidaemic participants were further divided into 33.3% (n=55) those with high
cholesterol, 29.1% (n=48) those with high triglycerides and 37.6% and (n= 62) those with
high cholesterol and triglycerides (mixed). The cohort comprised of 128 (52%) females,
median (IQR) age 56.0 (48.0 – 64.0) years and 116 (48%) males with median (IQR) age of
56.5 (48.0 – 63.0) years. Most of the characteristics between the dyslipidaemic and nondyslipidaemic participants were significantly different as expected in a purposive sampling
technique. ApoE3/4 genotype had the highest frequency distribution (41%) while ApoE2/3
genotype had the lowest frequency (7%). An uncharacterised ApoE referred to in the study as
ApoE X with a frequency distribution of 6%, was reported for the first time. The selected
measured parameters evaluated against a set of variables showed a significant association
between HbA1c and age (p=<0.008) is reported. TC (p=0.00092), LDL (p=0.0184) and TG
(p=0.0175) were strongly associated with poor glycaemic. Both LDL (p=0.0174 and HDL
(p=0.0072) were associated with age. Homozygous ApoE2/2 and heterozygous ApoE2/3
genotypes correlated with poor glycaemic control with a median HbA1c of 10.95% (IQR
5.88-14.98%) and 10.20% (IQR 6.20-15.80%), respectively; while homozygous ApoE4/4
carriers displayed good glycaemic control with a median HbA1c of 6.60% (IQR 5.70 –
2.30%). Carriers of homozygous ApoE3/3 genotype had the highest median TC of
6.06mmol/L (IQR 5.48 -– 6.71mmol/L) while homozygous ApoE4/4 carriers had the highest
median triglycerides of (2.94 (IQR 1.75 – 5.13 mmol/L). Carriers of homozygous PCSK9
rs505151 A/A (E670G) genotype had the highest frequency distribution in both groups of
participants with dyslipidaemic (55.1%) and non-dyslipidaemic (63. 5%), followed by
carriers of heterozygous PCSK9 rs505151G/A at 40.6% and lastly carriers of PCSK9
rs505151G/G at (9.5%). On the other hand, carriers of homozygous PCSK9 rs28362286 C/C
genotype were predominantly distributed with a frequency of 94.2% and
PCSK9rs28362286C/A had a very small frequency distribution of 5.8% while
PCSK9rs28362286A/A was absent in this population. Carriers of PCSK9 rs505151A/A
genotype had higher HbA1c with a median of 10.10% (IQR 7.48 – 12.90) compared to PCSK9 rs505151 G/A genotype with a median of 9.00% (IQR 7.03 –11.35). The results
show that PCSK9 rs505151G/A with lower HbA1c had non-significantly higher TC, LDL,
TG and non-HDL but lower HDL compared to PCSK9 rs505151A/A genotype. The results
revealed no direct reciprocal relationship between glycaemic control and level or type of
dyslipidaemia.
Conclusions: The study showed the effects of ApoE and PCSK9 genetic variation on the
dyslipidaemia seen in black South African diabetic participants. Therefore, this study through
ApoE and PCSK9 genotypes show that the diabetic dyslipidaemia has an underlying genetic
influence. In addition, to the well-characterised ApoE genotypes, an uncharacterised
genotype referred to as ApoE X genotype is reported. With these findings, consideration to
explore possible underlying genetic predisposition is recommended especially in diabetic
patients with dyslipidaemia that responds poorly to standard therapy.
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GAZZOTTI, MARTA. "FAMILIAL DYSLIPIDAEMIAS IN ITALY: SPECTRUM OF MUTATIONS, CLINICAL MANIFESTATIONS AND INFLUENCE OF ENVIRONMENTAL FACTORS." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/886428.
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Le dislipidemie genetiche rappresentano una delle principali cause di morbilità e mortalità cardiovascolare, tuttavia rimangono ancora sotto-stimate, sotto-diagnosticate e sotto-trattate nella popolazione generale. Negli ultimi anni, i registri di patologia si sono rivelati un utile strumento sia a livello nazionale che internazionale per affrontare queste problematiche. Il registro italiano delle dislipidemie è stato avviato attraverso lo studio LIPIGEN, il focus di questa tesi di dottorato, e ha iniziato la raccolta dei dati della dislipidemia genetica più frequente, rappresentata dall’ipercolesterolemia familiare (FH).
I principali scopi di questo progetto di tesi sono stati quelli di creare il primo registro italiano di FH, il cui modello possa essere esportato anche alle altre forme di dislipidemie genetiche, e di raccogliere dati real-world della situazione italiana che aiutassero ad identificare e superare eventuali criticità nell’identificazione e gestione della patologia. Da ciò è derivata la seconda parte della tesi, i cui scopi erano quelli di approfondire le discrepanze tra la diagnosi clinica e genetica, implementare la performance degli attuali algoritmi diagnostici disponibili, cercando anche di adattarli a specifiche sottopopolazioni come quella pediatrica.
Sulla base di questi obiettivi, i dati basali sono stati utilizzati per effettuare una completa caratterizzazione di adulti e bambini/adolescenti affetti da FH sia da un punto di vista clinico che genetico, e identificare i punti critici da sviluppare nella seconda parte della tesi. Per indagare il gap tra diagnosi clinica e genetica, è stata approfondita la natura poligenica di FH tra soggetti con diagnosi genetica positiva e negativa di FH. Questo studio ha permesso di confermare il ruolo dei polimorfismi a singolo nucleotide nella modulazione dei livelli di colesterolo LDL (c-LDL) non solo nei soggetti che non presentano una variante causativa di FH ma anche nei soggetti con mutazione monogenica, supportando l’applicazione dello score poligenico nell’implementazione della diagnosi e nella previsione del rischio cardiovascolare futuro.
Inoltre, il rilevamento della presenza di xantoma a livello del tendine di Achille tramite ecografia è stato identificato come un utile marker nella pratica clinica, supportando la sua introduzione negli algoritmi diagnostici per guidare i clinici nell'identificazione di soggetti FH con maggiore burden di c-LDL, che necessitano di essere trattati più precocemente possibile.
Inoltre, sono state indagate le principali differenze dei parametri utilizzati per la diagnosi clinica di FH tra gli adulti e i bambini/adolescenti, confermando la minor prevalenza dei tratti caratteristici di FH in quest’ultimo gruppo a causa dell’esposizione ancora limitata nel tempo ad elevati livelli di c-LDL. Ciò ha permesso di sottolineare l’importanza di stabilire criteri ad hoc per l’identificazione di FH in questa coorte, al fine di migliorare e standardizzare la gestione di FH nella popolazione pediatrica. Infine, sono stati riportati alcuni case report di pazienti affetti da altri disordini genetici, che costituiscono il punto di partenza per permettere l’apertura del registro LIPIGEN anche alle altre forme di dislipidemie genetiche.
In conclusione, lo sviluppo e la conduzione dello studio LIPIGEN hanno permesso di aumentare le conoscenze nell’ambito delle dislipidemie genetiche in Italia, di facilitare l’accesso all’esecuzione e all’interpretazione dei risultati genetici, di promuovere lo screening a cascata nei familiari dei soggetti affetti da FH e di partecipare ad iniziative internazionali per promuovere la gestione di FH a livello mondiale.Although genetic dyslipidemias are a common cause of cardiovascular morbidity and mortality, they are still underestimated, underdiagnosed and undertreated in the general population. To overcome these issues, disease registries are a useful tool at national and international levels. The Italian registry has been initiated through the LIPIGEN study, the focus of this PhD thesis, that started by focussing on the most frequent form of genetic dyslipidaemia: familial hypercholesterolemia (FH). The main aims of my PhD project were to create the first national registry of FH, that could be exported also to other genetic dyslipidemias, and to obtain real-world data of FH Italian population that would allow to identify and overcome obstacles in the detection, diagnosis, and treatments of FH. Subsequent objectives of the thesis were to better describe the discrepancies among clinical and genetic diagnosis, to improve the detection rate of diagnostic algorithm and to adapt them to specific sub-populations as the paediatric one. Based on these objectives, a full clinical and genetic characterization of both FH adults and children/adolescents was provided through the baseline data that were the starting point for the development of the second part of this thesis. Thus, to fill the gap between clinical and genetic diagnosis, the polygenic aetiology of FH was investigated among genetic negative and positive FH individuals, confirming the role of single nucleotide polymorphisms in the modulation of LDL-cholesterol (LDL-C) level even in monogenic Italian FH subjects, and supporting the use of a polygenic score in the refinement of diagnosis and in the prediction of future cardiovascular risk. Moreover, the Achilles tendon xanthoma detected by ultrasonography was identified as a valuable marker for clinical practice, supporting its introduction in the diagnostic algorithm to help physician in the identification of FH subjects with higher LDL-C burden, who require to be earlier and more aggressively treated. Furthermore, the main differences in the clinical diagnosis of FH between adults and children/adolescents were investigated, confirming the lower prevalence of the typical features of FH, which are associated to a long-life exposure to high levels of LDL-C, that is limited in young subjects. These findings support the need to establish ad hoc criteria for their identification, in order to improve and standardize the management of FH in the paediatric population. Finally, case reports of patients affected by other genetic disorders, setting the first steps for the extension of the LIPIGEN registry to other familial dyslipidemias, are reported. In summary, the development of the LIPIGEN study contributed to improve the knowledge of genetic dyslipidemias in Italy, to improve the access to the execution and interpretation of genetic results, to promote the process of cascade screening in the family members and to join international collaborations to face the burden of FH at global level.
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Evans, Jonathan. "APOE, PCSK9, and CETP genetic variants as potential biomarkers of dyslipidaemia in black South Africans with Type 2 Diabetes Mellitus." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29630.
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Dyslipidaemia is a commonly encountered clinical condition and is a major risk factor for cardiovascular diseases. Although there are many factors associated with dyslipidaemia, a strong genetic component is evident. Apolipoprotein E (APOE), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cholesteryl ester transfer protein (CETP) are key regulators of plasma cholesterol levels. Thus, genetic variation in the genes coding for these proteins contributes to dyslipidaemia. In this study, a cohort of black South African Type 2 Diabetes Mellitus (T2DM) patients was characterized for mutations in genes coding for APOE, PCSK9, and CETP, and the possible effects of these variants on their lipid profiles was evaluated. Participants (n=417) were recruited from the Chris Hani Baragwaneth Hospital Diabetes Clinic, Johannesburg from whom blood samples were obtained for DNA extraction. The cohort was further stratified into two groups; individuals on statin treatment (Sim+, n=291), and the second that was not on treatment (Sim-, n=87). Lipid profiles were determined by enzymatic methods. DNA was genotyped for APOE, PCSK9, and CETP variants using PCRRFLP and Sanger sequencing. Analysis of the effects of the genetic variants was carried out in two ways. Firstly, for all the participants combined, and then by separating those on statin treatment from those without (Sim+ vs. Sim-). Genotype and allele frequencies were calculated followed by genotype-phenotype correlations with lipid profiles. Univariate analysis showed a significant association between the APOE4 isoform and lower HDL-c levels in the combined cohort (p=0.034). The effects were more pronounced in the Sim- group (p=0.004) but were absent in the Sim+ group. Contrary to above, APOE2 was significantly associated with lower total cholesterol (TC) (p< 0.001) and lower LDL-c (p< 0.001) when compared to APOE3 in the combined cohort. Upon analysing treatment groups, the correlations were observed in the Sim+ group (p=0.027 and p=0.003, respectively), while there were no observed correlations in the Sim- group. The CETP rs34065661C/G and G/G genotypes were significantly associated with increased HDL-c levels (p=0.017; when applying a dominant genetic model) in the combined cohort, as well as in the Sim+ group (p=0.026). Multivariate analysis, using a generalized linear model, confirmed associations between APOE rs429358C and lower HDL-c (OR=0.881, p=1.64e04), and APOE rs7412T and decreased LDL-c (OR=0.759, p=0.012). No significant associations were observed for PCSK9 polymorphisms. We report significant associations between APOE and CETP genetic variations and altered lipid levels in this black South African T2DM population. These genetic variants could be biomarkers for dyslipidaemia among Africans. However, it is imperative that the APOE, PCSK9, and CETP genes are fully characterized for additional polymorphisms in order to come up with a better genetic profile that explains the variance in lipid levels observed in the black South African population. The impact of these genetic variants could be relevant to other black African populations as well.
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ALIEVA, ASIIAT. "GENETIC DYSLIPIDAEMIAS IN THE ITALIAN AND RUSSIAN POPULATIONS:FROM THE CLINIC TO THE BENCH." Doctoral thesis, Università degli Studi di Milano, 2022. http://hdl.handle.net/2434/916008.
Full textAbstract:
Genetic dyslipidemias are a heterogeneous group of disorders, and familial hypercholesterolemia (FH) is the most common one, that are characterized by abnormal levels of circulating lipoproteins and leading to premature cardiovascular diseases (CVD).
Despite the need for an accurate and timely diagnosis due to high cardiovascular risk of those patients
- there is still no well-managed system for a diagnosis and treatment of patients with severe dyslipidemias,
- there are still some gaps between clinical and genetic diagnosis scores that need to be improved to increase their reliability at the population level.
To overcome the above mentioned challenges, national registries on lipid disorders have been created as a tool to improve a screening programs and to make a progress towards formulating a joint consensus on methods to improve accuracy of its diagnosis and cardiovascular risk stratification.
The Italian and Russian Genetic Network (a background for the current PhD project) has been initiated with the primary focus on familial hypercholesterolemia as a genetically determined lipid disorder with the highest prevalence worldwide. The key goal of the current PhD thesis was to provide a phenotype – genotype characterization of the two populations aiming to use these data for searching of new approaches for improvement of an accuracy of FH diagnostics and cardiovascular risk stratification to promote in a future personalized approach in a disease management. The additional advantage of the current Network is an availability of a two-population validation of potential new markers for FH detection to will allow for an improvement of current algorithms.
Thus, we studied two cohorts from north cities of Italy and Russia (Milan and Saint Petersburg), a phenotype – genotype characterization for both cohorts was performed as well as concreate gaps between clinical and genetic diagnosis were described. The ultrasound measurement of Achilles tendon thickness was considered as a potential marker to fill in the gap between clinical and genetic FH diagnosis that brings an additional value to identification of FH subjects with higher LDL-C burden that may affect the level of the aggressiveness for the therapeutic strategies. Furthermore, proteomic data analysis demonstrated that a set of immune-inflammatory proteins associated with increased CVD risk, significantly characterize the clinically determined FH phenotype. Crossing the clinical phenotype with genetic analysis allowed to identify genetically positive FH individuals that, in addition to a higher LDL-C burden, were also characterized by a peculiar set of immune-inflammatory proteins as compared to genetically negative ones. By pairing genetically positive and negative FH patients for LDL-C levels, a number of significantly different proteins was indicated, that let to suggest that the prognostic value of these proteins should be longitudinally addressed.
In conclusion, the Italian and Russian Genetic Network contributed to reinforcing of knowledge about FH in both countries within the access to performing and interpretation of genetic results and analysis of approaches for an increase FH detection and risk stratification accuracy to driving improvement in standards of care for FH patients globally.
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Bloem, Johann. "A retrospective analysis of the prescribing patterns of hipolipidaemic drugs : a pharmacoeconomic approach / J. Bloem." Thesis, North-West University, 2009. http://hdl.handle.net/10394/4134.
Full textAbstract:
Background: More than 5.5 million South Africans aged 30 years and older are at risk of chronic disease by virtue of their triglyceride levels (Maritz, 2006:101). Dyslipidaemia is common in westernized and industrialized communities (Steyn et al., 2000:720), especially so for South Africa, where burden of disease data show dyslipidaemia to be the second most prevalent of all the chronic conditions in the country (Council for Medical Schemes, 2006:48). It is therefore no surprise that at 3.3 per cent hipolipidaemics ranked second highest based on prevalence percentage per therapeutic group in the 2005 Mediscor medicines review on South African medical claims data (Bester et al., 2005:8-11). Hipolipidaemic drugs subsequently also ranked second highest for expenditure per therapeutic group, achieving a total expenditure of 5.8 per cent.
Objective: The purpose of this study was to characterise the usage and cost of hipolipidaemic drugs in the private health care environment in South Africa based on various categories, including age, sex, prescriber type and generic indicator.
Methods: A quantitative retrospective drug utilisation review was performed using dispensing records from a medicine claims database. Data for a two-year period (1 Jan. 2005 to 31 Dec. 2006) were used. Hipolipidaemic medicine usage was analysed according to five patient age strata: patients younger than 9 years, 10 ≤ 19 years, 20 ≤ 45 years, 46 ≤ 59 years and older than 59 years.
Basic descriptive statistics such as frequencies and arithmetic mean (average) were used to characterise the study sample, and were calculated using the Statistical Analysis System (SAS®) for Windows 9.1® program (SAS Institute Inc., 2002-2003).
Results: The database consisted of 19 860 593 and 21 473 062 medicine item claims for 2005 and 2006 respectively, at a total cost of R 1 893 376 921.00 (for 2005) and R2 046 944 383.00 (for 2006). Patients receiving hipolipidaemic medicine items represented about 7.2% of the
total number of patients on the database in both 2005 and 2006. About 47% of the study population in both 2005 and 2006 was female, compared to 53% males.
Hipolipidaemics represented between 3.1% (N = 19 860 593) and 3.3% (N = 21 473 062) of the total number of items claimed during the study period. The total cost of hipolipidaemics accounted for between 5.6% (N = R1 893 376 921.00) and 5.8% (N = R2 046 944 383.00) of the total cost of all medications claimed during the study period. The average cost per item of hipolipidaemics was R170.63 ± 70.19 in 2005 compared to R167.08 ± 71.93) in 2006. HMG-CoA reductase inhibitors formed the leading therapeutic class in hipolipidaemic medicine items in all age groups on the database, except for children aged 0 ≤ 9 years, where the “others” group, in particular cholestyramine (Questran Lite 4 mg) was claimed more frequently. Of the items claimed for both study periods, simvastatin was the most commonly claimed, accounting for 45.35% (n = 284 232) and 46.21% (n = 325 970) respectively of the number of hipolipidaemic items claimed, at a total cost of 30.97% (n = R33 119 294.18) and 31.38% (n = R36 983 938.41) for 2005 and 2006 respectively.
Non-substitutable and generic hipolipidaemic medicine items carried the largest percentage of prevalence and cost in both study periods for both sex categories and all age groups. The majority of claims for hipolipidaemic medicine items were prescribed by general medical practitioners, followed by “other prescribers” and then by cardiologists. Only a small number of prescriptions claimed were prescribed by thoracic surgeons and even fewer by pharmacotherapists and pharmacists. Trade name products that were mostly prescribed were Lipitor and Adco-Simvastatin.
Of all the hipolipidaemic drugs utilised on the database, only three active ingredients (bezafibrate, simvastatin and pravastatin) had generic equivalents available at the time of the study. With total substitution (100%) of these three drugs with the average price of the available generic hipolipidaemic equivalents on the database, a cost saving of R1 744 462.27 or 1.63% (N = R106 943 348.53) was possible in 2005. In 2006, a total cost saving of R1 526 985.79 or 1.30% (N = R117 862 631.87) was calculated.
Conclusion: The study highlighted the most commonly prescribed hipolipidaemics within a sub-population of South African patients. The high average cost per prescription of hipolipidaemic drugs indicates that they are relatively expensive in comparison to other medications. Generic (and therapeutic) substitution should be investigated as potential cost-saving mechanisms in the private health care sector of South Africa.Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2010.
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"Genetic and biochemical aspects of dyslipidaemias in Chinese." 2001. http://library.cuhk.edu.hk/record=b6073364.
Full textAbstract:
Ma Yanqing.Thesis (Ph.D.)--Chinese University of Hong Kong, 2001.
Includes bibliographical references (p. 279-324).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.
Abstracts in English and Chinese.
Books on the topic "Genetic dyslipidaemia"
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Jolly, Elaine, Andrew Fry, and Afzal Chaudhry, eds. Endocrine. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199230457.003.0007.
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Chapter 7 covers the basic science and clinical topics relating to the endocrine system which trainees are required to learn as part of their basic training and demonstrate in the MRCP. It covers endocrine physiology, acid-base balance, thyrotoxicosis, hypothyroidism, goitre and thyroid nodule, Cushing syndrome, acromegaly, hyperprolactinaemia, hypopituitarism, diabetes insipidus, adrenal incidentaloma, primary hyperaldosteronism, adrenal insufficiency, phaeochromocytoma and paraganglioma , male hypogonadism and Gynaecomastia, menstrual disorders and anovulation, hirsutism and the polycystic ovarian syndrome, multiple endocrine neoplasia and other genetic endocrine tumour syndromes, neuroendocrine tumours, acid-base disorders, sodium disorders, potassium disorders, hypocalcaemia, hypercalcaemia, hyperparathyroidism, osteoporosis, osteomalacia, Paget disease, dyslipidaemia, porphyria, adult inborn errors of metabolism, and obesity.
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Dalbeth, Nicola. Gout. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0141.
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Gout is a common and treatable disorder of purine metabolism. Gout typically presents as recurrent self-limiting episodes of severe inflammatory arthritis affecting the foot. In the presence of persistent hyperuricaemia, tophi, chronic synovitis, and joint damage may develop. Diagnosis of gout is confirmed by identification of monosodium urate (MSU) crystals using polarizing light microscopy. Hyperuricaemia is the central biochemical cause of gout. Genetic variants in certain renal tubular urate transporters including SLC2A9 and ABCG2, and dietary factors including intake of high-purine meats and seafood, beer, and fructose, contribute to development of hyperuricaemia and gout. Gout treatment includes: (1) management of the acute attack using non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or low-dose colchicine; (2) prophylaxis against gout attacks when commencing urate-lowering therapy (ULT), with NSAIDs or colchicine; and (3) long-term ULT to achieve a target serum urate of less than 0.36 mmol/litre. Interleukin (IL)-1β is a central mediator of acute gouty inflammation and anti-IL-1β therapies show promise for treatment of acute attacks and prophylaxis. The mainstay of ULT remains allopurinol. However, old ULT agents such as probenecid and benzbromarone and newer agents such as febuxostat and pegloticase are also effective, and should be considered in patients in whom allopurinol is ineffective or poorly tolerated. Management of gout should be considered in the context of medical conditions that frequently coexist with gout, including type 2 diabetes, hypertension, dyslipidaemia, and chronic kidney disease. Patient education is essential to ensure that acute gout attacks are promptly and safely managed, and long-term ULT is maintained.
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Dalbeth, Nicola. Gout. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199642489.003.0141_update_003.
Full textAbstract:
Gout is a common and treatable disorder of purine metabolism. Gout typically presents as recurrent self-limiting episodes of severe inflammatory arthritis affecting the foot. In the presence of persistent hyperuricaemia, tophi, chronic synovitis, and joint damage may develop. Diagnosis of gout is confirmed by identification of monosodium urate (MSU) crystals using polarizing light microscopy. Hyperuricaemia is the central biochemical cause of gout. Genetic variants in certain renal tubular urate transporters including SLC2A9 and ABCG2, and dietary factors including intake of high-purine meats and seafood, beer, and fructose, contribute to development of hyperuricaemia and gout. Gout treatment includes: (1) management of the acute attack using non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or low-dose colchicine; (2) prophylaxis against gout attacks when commencing urate-lowering therapy (ULT), with NSAIDs or colchicine; and (3) long-term ULT to achieve a target serum urate of less than 0.36 mmol/litre. Interleukin (IL)-1β is a central mediator of acute gouty inflammation and anti-IL-1β therapies show promise for treatment of acute attacks and prophylaxis. The mainstay of ULT remains allopurinol. However, old ULT agents such as probenecid and benzbromarone and newer agents such as febuxostat and pegloticase are also effective, and should be considered in patients in whom allopurinol is ineffective or poorly tolerated. Management of gout should be considered in the context of medical conditions that frequently coexist with gout, including type 2 diabetes, hypertension, dyslipidaemia, and chronic kidney disease. Patient education is essential to ensure that acute gout attacks are promptly and safely managed, and long-term ULT is maintained.
Book chapters on the topic "Genetic dyslipidaemia"
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Romeo, Stefano, Bo Angelin, and Paolo Parini. "Genetic Forms of Dyslipidaemia." In Oxford Textbook of Endocrinology and Diabetes 3e, edited by John A. H. Wass, Wiebke Arlt, and Robert K. Semple, 1868–77. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198870197.003.0231.
Full textAbstract:
While monogenic diseases are typically considered rare, elevated lipoprotein levels due to single sequence variants are fairly common, with, for example, the prevalence of familial hypercholesterolaemia being as high as 1 in 250 in the general population. Identification of such monogenic disorders and formal genetic diagnosis is imperative to tailor treatment and to pre-empt complications in family members carrying pathogenic mutations. Dyslipidaemias may be ‘primary’ and genetic, in which severe dyslipidaemia is the inevitable result of an underlying genetic mutation, and these will be the main focus of this chapter. This chapter also aims to provide an accessible account of known monogenic disorders causing hyperlipidaemia, with a focus on diagnosis and treatment.
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Guha, NG. "Genetic assessment of dyslipidaemia (revision number 4)." In Diapedia. Diapedia.org, 2014. http://dx.doi.org/10.14496/dia.6104914166.4.
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Cegla, Jaimini, and James Scott. "Lipid disorders." In Oxford Textbook of Medicine, edited by Timothy M. Cox, 2055–97. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0232.
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High blood cholesterol and high blood triglycerides are causal risk factors for atherosclerotic cardiovascular disease, which remains the leading cause of death in the developed world. Lipid and lipoprotein metabolism—cholesterol, triglycerides, and fat-soluble vitamins are transported with specific proteins in the blood as multimeric complexes called lipoproteins. Lipid and lipoprotein metabolism are effected by three principal physiological processes: (1) intestinal absorption of dietary lipid and transport in the blood of dietary lipid and lipids, principally derived from the liver (as triglyceride-rich lipoproteins) to peripheral tissues for catabolism by skeletal and cardiac muscle or storage in adipose tissue; (2) return of triglyceride-rich lipoprotein remnants to the liver, hepatic synthesis of low-density lipoprotein, and the transport of cholesterol between peripheral tissues and the liver; and (3) reverse cholesterol transport by high-density lipoprotein (HDL) between peripheral tissues and the liver. Dyslipidaemias are disorders of lipoprotein metabolism in which there is elevation of total cholesterol and/or triglycerides, often accompanied by reduced levels of HDL cholesterol. Causes of dyslipidaemia—particular lipid disorders including polygenic hypercholesterolaemia, familial hypercholesterolaemia, combined hypercholesterolaemia and hypertriglyceridaemia, familial combined hyperlipidaemia, familial dysbetalipoproteinaemia (also called type 3 hyperlipoproteinaemia), and severe hypertriglyceridaemia, as well as secondary or aggravating factors. Management of dyslipidaemia—the key questions are: (1) what classes of lipoproteins and lipids are increased or decreased in the patient’s plasma? (2) Does the patient has a primary (genetic) or secondary (acquired) dyslipidaemia (often contributions from both influences)? (3) Is the patient at risk of atherosclerotic cardiovascular disease or acute pancreatitis? (4) What other risk factors (e.g. hypertension or diabetes) are present? (5) What treatments might be used to address these abnormalities?
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Stewart, Stephen F., and Chris P. Day. "Nonalcoholic steatohepatitis." In Oxford Textbook of Medicine, 2480–82. Oxford University Press, 2010. http://dx.doi.org/10.1093/med/9780199204854.003.152202_update_001.
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Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in the developed world, affecting 20 to 30% of Western adults. Nonalcoholic liver disease occurs with a range of severity from simple steatosis through nonalcoholic steatohepatitis (NASH) to fatty fibrosis—and, ultimately, cirrhosis. The condition is a manifestation of the metabolic syndrome, strongly associated with obesity, insulin resistance, and dyslipidaemia; dietary and genetic factors appear to determine susceptibility to the disease and its progression....
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Schunkert, Heribert. "Complex cardiovascular diseases: atherosclerosis—genetic factors." In ESC CardioMed, 723–25. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0163.
Full textAbstract:
The elucidation of genetic mechanisms affecting the risk of atherosclerosis has largely benefited from recent technological breakthroughs in terms of high-throughput sequencing and genotyping. While a decade ago only a positive family history and mutations causing familial hypercholesterolaemia were proven to confer genetic risk of atherosclerosis, by now multiple genes have been implicated in monogenic and complex forms of accelerated atherosclerosis. At the population level, the discovery of hundreds of common variants, each affecting the risk of atherosclerosis by a small margin, may have even broader implications. A substantial finding from these studies is that the risk of atherosclerosis and its clinical manifestations, such as myocardial infarction, stroke, and peripheral arterial disease, is secondary to a much broader spectrum of underlying (genetic) mechanisms than previously thought, when only the classical risk factors, such as hypertension, dyslipidaemia, diabetes mellitus, and smoking were implicated in the disease aetiology. Currently, the systems biology of the multiple interacting factors contributing to the risk of atherosclerosis as well as respective therapeutic implications, in part addressed by Mendelian randomization studies, is subject to intensive research. Likewise, genetic risk scores are scrutinized to improve the prediction of coronary artery disease in asymptomatic individuals. This chapter gives a brief overview on the current understanding of the genetic underpinnings of atherosclerosis.
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Schunkert, Heribert. "Complex cardiovascular diseases: atherosclerosis—genetic factors." In ESC CardioMed, 723–25. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0163_update_001.
Full textAbstract:
The elucidation of genetic mechanisms affecting the risk of atherosclerosis has largely benefited from recent technological breakthroughs in terms of high-throughput sequencing and genotyping. While a decade ago only a positive family history and mutations causing familial hypercholesterolaemia were proven to confer genetic risk of atherosclerosis, by now multiple genes have been implicated in monogenic and complex forms of accelerated atherosclerosis. At the population level, the discovery of hundreds of common variants, each affecting the risk of atherosclerosis by a small margin, may have even broader implications. A substantial finding from these studies is that the risk of atherosclerosis and its clinical manifestations, such as myocardial infarction, stroke, and peripheral arterial disease, is secondary to a much broader spectrum of underlying (genetic) mechanisms than previously thought. Indeed, the genetic variants leading to atherosclerosis go far beyond the effects of classical risk factors, such as hypertension, dyslipidaemia, diabetes mellitus, and smoking. Based on these findings, genetic risk scores are scrutinized to improve the prediction of coronary artery disease in asymptomatic individuals. Remarkably, people with a high genetic risk burden have the greatest benefit from therapeutic lowering of LDL cholesterol. Currently, the systems biology of the multiple interacting factors contributing to the risk of atherosclerosis as well as respective therapeutic implications, in part addressed by Mendelian randomization studies, is subject to intensive research. Likewise, genetic risk scores are scrutinized to improve the prediction of coronary artery disease in asymptomatic individuals. This chapter gives a brief overview on the current understanding of the genetic underpinnings of atherosclerosis.
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Angelin, Bo, and Paolo Parini. "Lipoprotein Metabolism." In Oxford Textbook of Endocrinology and Diabetes 3e, edited by John A. H. Wass, Wiebke Arlt, and Robert K. Semple, 1859–68. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198870197.003.0230.
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Lipids are a heterogeneous group of substances with a myriad of structural and regulatory functions. The realization that changes in plasma lipids, particularly elevated cholesterol in apolipoprotein B-containing lipoproteins, are associated with an increased risk of cardiovascular disease has given great impetus to the study of factors regulating plasma lipid metabolism. With the use of increasingly refined methodology, understanding of normal plasma lipoprotein metabolism and its derangements in the face of genetic and/or environmental factors is continuously expanding. This chapter summarizes current concepts regarding normal plasma lipoprotein synthesis, transport, and interconversion in humans, forming a basis for subsequent discussions of pathogenesis, diagnosis, and treatment of dyslipidaemia.
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Swerdlow, Daniel I., Steve E. Humphries, and Michael V. Holmes. "Complex cardiovascular diseases: dyslipidaemias—genetic factors." In ESC CardioMed, 725–30. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0164.
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The genetics of rare familial hyperlipidaemias have been studied for many years, but the last decade has seen major advances in our understanding of the genetics of common dyslipidaemias. These developments have largely been propelled by the rapid innovations in genotyping and phenotyping technologies. Genome-wide association, whole exome sequencing, and whole genome sequencing studies have identified a large number of genetic loci involved in lipid metabolism. Large-scale meta-analyses have included over 150,000 individuals, increasing statistical power to identify rarer variants, and common variants with smaller phenotypic effects. Furthermore, advances in phenotyping such as nuclear magnetic resonance-based lipidomics have facilitated finer mapping of circulating lipids and lipoproteins. Capitalizing on the findings from these large-scale studies, genetic analyses using the Mendelian randomization principle have been used successfully to explore the causal contributions to heart disease of a range of circulating lipid fractions. Such investigations have confirmed a causal role for low-density lipoprotein cholesterol, suggest a causal role for triglycerides, but cast doubt on that of high-density lipoprotein cholesterol. Furthermore, genetic studies have been shown to have an important application in the validation of novel therapeutic targets for treatment of dyslipidaemias.
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Cheung, Bernard M. Y., and Esther W. Chan. "Ethnic differences in responses to cardiovascular drugs." In ESC CardioMed, edited by Gregory Lip, 2908–10. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0704.
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Ethnic differences in therapeutic response or adverse reactions may be due to genetic factors, differences in body composition, and diet. Black individuals tend to be more responsive to thiazides and less so to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers. The risk of angio-oedema with ACEIs is increased. In contrast, the isosorbide–hydralazine combination is approved for treating heart failure only in black patients. Chinese patients have a higher incidence of ACEI-induced cough. They are more susceptible to myositis with high-dose statins. A proportion of Asian patients have poor cytochrome P450 2C19 activity and are less capable of metabolizing clopidogrel to its active form. The target international normalized ratio for Chinese patients is also 2–3, but the maintenance dose of warfarin is usually lower than in Caucasians. Regardless of ethnicity, control of hypertension and dyslipidaemia, and antiplatelet therapy all help to reduce cardiovascular complications. Attention to dose, interacting drugs, and pharmacogenetics should help to make drugs safer in every ethnic group.
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Anstee, Quentin M., and Christopher P. Day. "Nonalcoholic fatty liver disease." In Oxford Textbook of Medicine, edited by Jack Satsangi, 3147–55. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0328.
Full textAbstract:
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in the developed world, affecting 20 to 30% of Western adults. Nonalcoholic liver disease occurs with a range of severity from simple steatosis through nonalcoholic steatohepatitis (NASH) to fatty fibrosis and, ultimately, cirrhosis. The condition is a manifestation of the metabolic syndrome, strongly associated with obesity, insulin resistance, and dyslipidaemia. Dietary and genetic factors appear to determine susceptibility to the disease and its progression. In most patients, the condition is discovered incidentally when abnormal values of serum liver-related liver tests are reported. The diagnosis is usually one of exclusion. Liver biopsy is not always required but, in the absence of well-validated noninvasive biomarkers, remains the only way to detect steatohepatitis and accurately stage fibrosis of intermediate severity. However, biopsy is not practical in all cases and so a staged approach to patient assessment and risk stratification is advised. Treatment is directed at components of the metabolic syndrome: weight loss through diet and exercise has been shown to ameliorate disease. A range of novel pharmacological drug treatments are under evaluation.
Conference papers on the topic "Genetic dyslipidaemia"
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Mészáros, Martina, Ádám D. Tárnoki, Dávid L. Tárnoki, Dániel Kovács, Bianka Forgó, Jooyeon Lee, László Kunos, and András Bikov. "OSA, hypertension, diabetes and dyslipidaemia share common genetic background: Results of a twin study." In ERS International Congress 2019 abstracts. European Respiratory Society, 2019. http://dx.doi.org/10.1183/13993003.congress-2019.pa881.
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Anghel, Lucretia, Dumitru Ursu, Simona Mitincu Caramfil, Cristina Stefanescu, Stefana Maria Moisa, Anamaria Ciubara, and Liliana Baroiu. "THE LINK BETWEEN LIPIDIC PROFILE, DEPRESSION AND CARDIOVASCULAR DISEASE." In The European Conference of Psychiatry and Mental Health "Galatia". Archiv Euromedica, 2023. http://dx.doi.org/10.35630/2022/12/psy.ro.17.
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The purpose of this study was to identify the connection between cardiovascular disease and depression taking lipid profile as a common risk factor in the occurrence of both pathologies. Materials and methods: 100 patients were examined for 3 months, admitted to the internal medicine department of St. Andrew's Emergency Hospital in Galati. Anamnesis was collected; electrocardiogram, objective examination and lipid profile were performed. The Hamilton scale (HDRS-17) was used to assess depression. Results: In patients with depression, an increased prevalence of dyslipidaemia and obesity was detected, especially in women. Of 10 women with mild and severe depression, all had altered lipid profile, obesity or overweight and increased risk of cardiovascular disease. Conclusions: Although it is claimed that depression would be an individual risk factor for the occurrence of an adverse cardiac event, the comprehensive pathophysiological approach allows the identification of risk factors for both CVD and depression as being largely common. Therefore, a coexistence relationship is created. The other possible situations may arise due to the involvement of individual protective factors and genetic vulnerability. As a result, treatment of depression may reduce risk of cardiovascular event in some cases.