Dataset Information

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

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 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.

SUBMITTER: Polisecki E

PROVIDER: S-EPMC2853447 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Polisecki Eliana E Peter Inga I Simon Jason S JS Hegele Robert A RA Robertson Michele M Ford Ian I Shepherd James J Packard Christopher C Jukema J Wouter JW de Craen Anton J M AJ Westendorp Rudi G J RG Buckley Brendan M BM Schaefer Ernst J EJ

Journal of lipid research 20090914 5

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 ...[more]

PMID: 19752398

Similar Datasets

Project description:Background Single nucleotide polymorphisms (SNPs) in the EPHX2 gene have been implicated in susceptibility to cardiovascular diseases, including coronary heart disease (CHD). EPHX2 encodes for soluble epoxide hydrolase, an important enzyme involved in the metabolic breakdown of arachidonic acid-derived vasoactive and anti-inflammatory eicosanoids referred to as epoxyeicosatrienoic acids to their corresponding diols. Our pilot study aimed to investigate whether common SNPs such as rs751141, rs4149253, and rs1042064 of the EPHX2 gene are associated with susceptibility to CHD in Russian population. Methods A total of 1,183 unrelated Russian subjects comprising 602 patients with angiographically diagnosed CHD and 581 age- and sex-matched healthy subjects were recruited and their DNA samples were genotyped for the selected SNPs using a high-throughput Mass-ARRAY genotyping platform. Results No significant associations were found between the investigated SNPs and CHD risk (P>0.05). A polymorphism rs751141 (amino acid substitution, R287Q) displayed a trend towards association with CHD (odds ratio adjusted by sex and age was 3.02, 95% CI: 0.97–9.43, P correction =0.16). SNP-smoking interaction analyses did not identify synergic effects of the studied SNPs and cigarette smoking on the disease risk (P>0.05). A linkage disequilibrium was found between SNPs rs751141 and rs4149253 (D’ =0.995), rs751141 and rs1042064 (D’ =0.967), rs4149253 and rs1042064 (D’ =0.965). Four common haplotypes G-G-T (73%), A-G-C (10%), G-G-C (9%) and G-A-C (7%) have been identified, however, none of them showed a significant association with the risk of CHD in the studied population (P>0.05). Conclusions The investigated polymorphisms do not contribute to CHD susceptibility in our population. Nevertheless, because of a limited number of SNPs was investigated in this study, definitive conclusions yet to be made in further studies on the contribution of the EPHX2 gene to the development of CHD in Russians.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets