出版社：American Society for Biochemistry and Molecular Biology
摘要：Niemann-Pick C1-like 1 protein (NPC1L1) plays a critical role in intestinal cholesterol absorption. Our objective was to examine whether five variants (-133A>G, -18A>C, L272L, V1296V, and U3_28650A>G) at the NPC1L1 gene have effects on lipid levels, prevalence, and incidence of coronary heart disease (CHD) and lipid-lowering response to pravastatin. We studied 5,804 elderly participants from the PROSPER study, who were randomized to pravastatin 40 mg/day or placebo and were followed on average for 3.2 years. In the adjusted gender-pooled analyses, homozygous carriers of the minor alleles at four NPC1L1 sites (-18A>C, L272L, V1296V, and U3_28650A>G, minor allele frequencies 0.15–0.33) had 2–8% higher LDL-cholesterol (LDL-C) levels at baseline than homozygous carriers of the common alleles ( P P G polymorphism and not other variants was associated with 6 month LDL-C lowering ( P = 0.02). Our data indicate that variation in the NPC1L1 gene is associated with plasma total and LDL-C levels and CHD risk.
关键词：statins ; single nucleotide polymorphism ; low density lipoprotein ; coronary heart disease ; cholesterol absorption
