Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/109589

In Collections

This item can be found in the following collections:

Polisecki, E.; Peter, I.; Simon, J.S.; Hegele, R.A.; Robertson, M.; Ford, I.; ... ; Prospective Study Pravastatin Elde (2010)

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

Article / Letter to editor
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....Show moreNiemann-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.-Polisecki, E., I. Peter, J. S. Simon, R. A. Hegele, M. Robertson, I. Ford, J. Shepherd, C. Packard, J. W. Jukema, A. J. M. DeCraen, R. G. J. Westendorp, B. M. Buckley, and E. J. Schaefer. Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart disease risk in the elderly. J. Lipid Res. 2010. 51: 1201-1207.Show less
statins single nucleotide polymorphism low density lipoprotein coronary heart disease cholesterol absorption apolipoprotein-e genotype cholesterol absorption serum cholestanol ezetimibe atorvastatin polymorphism homeostasis pravastatin prediction sterols
All authors
Polisecki, E.; Peter, I.; Simon, J.S.; Hegele, R.A.; Robertson, M.; Ford, I.; Shepherd, J.; Packard, C.; Jukema, J.W.; Craen, A.J.M. de; Westendorp, R.G.J.; Buckley, B.M.; Schaefer, E.J.; Prospective Study Pravastatin Elde
Date
2010-05-31
Journal
Journal of Lipid Research
Volume
51
Issue
5
Pages
1201 - 1207
DOI
doi:10.1194/jlr.P001172