Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart disease risk in the elderly

Polymorphisms of the Niemann-Pick C1-like 1 gene in a Japanese population

“…The minor allele 1735G has been reported to be associated with relatively higher TC and LDL-C levels in a European population, while 1735GG carriers showed higher LDL-C levels as compared to CC and CG carriers (17). In their study Maeda et al (20) demonstrated that the campesterol level, a marker of cholesterol absorption, was significantly higher in the GG vs. the CG/CC genotypes in a Japanese population.…”

“…Multiple rare sequence variants in the NPC1L1 gene have recently been found to be associated with variations in cholesterol absorption and plasma cholesterol levels (12,13,16,17). In their study, Cohen et al (18) identified a series of non-synonymous sequence variations of NPC1L1 associated with high or low cholesterol absorption using the campesterol:lathosterol ratio as a surrogate marker of cholesterol absorption (18).…”

Single-nucleotide polymorphisms: a perspective of cardiovascular prevention

“…The results suggest that polymorphism in the gene SCAP 2386A>G was a significant predictor of response to treatment with statin for levels of total cholesterol and TGC. In the same line of study, Poliseckil et al 12 evaluated the effects on lipid levels and prevalence/incidence of CAD as well as response to pravastatin in reducing plasma lipid profile, and the five variants of the Niemann-Pick C1-lie 1 (NPC1L1) gene. The findings of the study indicate that variations in the NPC1L1 protein gene are associated with the levels of LDL-c and risk of cardiovascular disease.…”

“…This variation may be due to environmental factors such as body weight, smoking, diet and drugs, but also due to genetic polymorphisms involved in lipoprotein metabolism. 4,7 The different responses to statins in reducing plasma lipid profile 12 also play an important role in monitoring the dyslipidemic patient.…”

Ezetimibe

“…8,10 Common single nucleotide polymorphisms (SNPs) in NPC1L1 are associated with variation in both LDL cholesterol concentrations and response to ezetimibe. [11][12][13] Homozygous carriers of the minor alleles of 5 previously reported NPC1L1 single nucleotide polymorphisms had 2% to 8% higher LDL cholesterol levels and increased risk of coronary artery disease (CAD) events during the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. 12 These included a synonymous coding variant, rs2072183, identified by the Global Lipids Consortium, whose minor alleles increased LDL cholesterol by 2.0 mg/dL.…”