Polisecki, E. et al. (2010) Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart disease risk in the elderly. Journal of Lipid Research, 51(5), pp. 1201-1207. (doi: 10.1194/jlr.P001172)
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Abstract
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 < 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.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Robertson, Mrs Michele and Shepherd, Prof James and Ford, Professor Ian and Packard, Professor Chris |
Authors: | Polisecki, E., Peter, I., Simon, J.S., Hegele, R.A., Robertson, M., Ford, I., Shepherd, J., Packard, C., Jukema, J.W., de Craen, A.J.M., Westendorp, R.G.J., Buckley, B.M., and Schaefer, E.J. |
Subjects: | R Medicine > R Medicine (General) |
College/School: | College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre ?? 20206000 ?? College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Journal of Lipid Research |
ISSN: | 0022-2275 |
Published Online: | 14 September 2009 |
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