Familial hypercholesterolemia (FH) is an autosomal disorder characterized by increased levels of total cholesterol and low density lipoprotein cholesterol. The FH clinical phenotype has been shown to be associated with increased coronary heart disease and premature death. Mutations in the low density lipoprotein receptor gene (LDLR) can result in the FH phenotype, and there is evidence that receptor-negative mutations result in a more severe phenotype than do receptor-defective mutations. Mutations in the apolipoprotein B-100 gene (APOB) can result in a phenotype that is clinically indistinguishable from familial hypercholesterolemia, and mutations in this gene have also been shown to be associated with coronary heart disease. Preliminary research indicates that the FH phenotype is influenced by other genetic and environmental factors; however, it is not clear if these are synergistic interactions or simply additive effects.
"Familial hypercholesterolemia (FH) is a disorder of lipid metabolism associated with a severe risk of cardiovascular disease (CVD)  . Effective CVD prevention is available, consisting of lifestyle changes and lifelong statin treatment  . "
[Show abstract][Hide abstract] ABSTRACT: Purpose: This study assesses the success of the recently terminated Dutch nationwide cascade screening
by examining whether children with familial hypercholesterolemia (FH) were identified through family
screening or due to cardiovascular (CVD) events in the FH parent.
Methods: We collected clinical information of all children (0e18 years) with FH with a pathogenic
variant at our outpatient lipid clinic between 1992 and 2014 and their FH parents and FH grandparents.
Results: We analysed 292 FH children from 205 parents with FH. A history of premature CVD was present
in 20% of the parents (29% of the fathers, 9% of the mothers) and 49% of the FH grandparents.
Conclusion: The fact that CVD is still a presenting event of FH in especially fathers shows that nationwide
screening might have been terminated too early. Therefore we recommend to proceed the cascade
"Previous studies and clinical trials have established multiple risk factors contributing to the pathogenesis of MI, including obesity, hypercholesterolemia, smoking, alcohol intake, diabetes, hypertension, physical inactivity and psychosocial situation [1-3]. Among these, hypercholesterolemia arising from abnormal lipid metabolism has been considered to be one of the most key risk factors for MI [4,5]. What’s more, apart from above modifiable risk factors, a growing body of studies have demonstrated close associations of genetic variants in candidate genes with the risk of MI, suggesting that host genetic backgrounds exert critical roles on MI pathogenesis as well [6-8]. "
[Show abstract][Hide abstract] ABSTRACT: Background
Abnormal lipids is one of the critical risk factors for myocardial infarction (MI), however the role of genetic variants in lipid metabolism-related genes on MI pathogenesis still requires further investigation. We herein genotyped three SNPs (LRP6 rs2302685, LDLRAP1 rs6687605, SOAT1 rs13306731) in lipid metabolism-related genes, aimed to shed light on the influence of these SNPs on individual susceptibility to MI.
Genotyping of the three SNPs (rs2302685, rs6687605 and rs13306731) was performed in 285 MI cases and 650 control subjects using polymerase chain reaction–ligation detection reaction (PCR–LDR) method. The association of these SNPs with MI and lipid profiles was performed with SPSS software.
Multivariate logistic regression analysis showed that C allele (OR = 1.62, P = 0.039) and the combined CT/CC genotype (OR = 1.67, P = 0.035) of LRP6 rs2302685 were associated with increased MI risk, while the other two SNPs had no significant effect. Further stratified analysis uncovered a more evident association with MI risk among younger subjects (≤60 years old). Fascinatingly, CT/CC genotype of rs2302685 conferred increased LDL-C levels compared to TT genotype (3.0 mmol/L vs 2.72 mmol/L) in younger subjects.
Our data provides the first evidence that LRP6 rs2302685 polymorphism is associated with an increased risk of MI in Chinese subjects, and the association is more evident among younger individuals, which probably due to the elevated LDL-C levels.
Lipids in Health and Disease 06/2014; 13(1):94. DOI:10.1186/1476-511X-13-94 · 2.22 Impact Factor
"The extent of mutation of LDLR genes is also a major factor that determines the natural course of heterozygous FH patients. However, uncontrolled risk factors for cardiovascular diseases such as smoking, hypertension and diabetes mellitus increase the risk considerably.7) It was reported that the attack rate of myocardial infarction in unidentified and untreated FH males and females before the age of sixty was sixty percent and thirty percent or greater, respectively. "
[Show abstract][Hide abstract] ABSTRACT: Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular diseases, and is inherited as an autosomal dominant trait. The prevalence of heterozygous FH is one in five hundred people. Owing to dysfunctional low density lipoprotein (LDL) receptors due to genetic mutations, serum low density lipoprotein-cholesterol (LDL-C) levels are considerably increased from birth. FH is clinically diagnosed by confirmation of family history and characteristic findings such as tendon xanthoma or xanthelasma. Thus, clinical concern and suspicion are important for early diagnosis of the disease. Current guidelines recommend lowering LDL-C concentration to at least 50% from baseline. Statins are shown to lower LDL-C levels with high safety, and thus, have been the drug of choice. However, it is difficult to achieve an ideal level of LDL-C with a single statin therapy in the majority of FH patients. Alternatively, lipid lowering combination therapy with the recently-introduced ezetimibe has shown more encouraging results.
Korean Circulation Journal 06/2013; 43(6):363-7. DOI:10.4070/kcj.2013.43.6.363 · 0.75 Impact Factor
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