Cited 32 times since 2009 (2.2 per year) source: EuropePMC Journal of lipid research, Volume 51, Issue 5, 14 2 2009, Pages 1201-1207 Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart disease risk in the elderly. Polisecki E, Peter I, Simon JS, Hegele RA, Robertson M, Ford I, Shepherd J, Packard C, Jukema JW, de Craen AJ, Westendorp RG, Buckley BM, Schaefer EJ, Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) Investigators
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 prava-statin 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 < 0.05). Homozygotes for the rare alleles also had a significant increase in the risk of CHD events on trial (range of hazard ratios 1.50-1.67; P < 0.02), regardless of the treatment regimen. The -133 A>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.
