Relative contributions of genes, environment, and interactions to blood lipid concentrations in a general adult population.

The authors evaluated the contributions of nine genetic (G) variants (selected from 275 single nucleotide polymorphisms in 11 reverse cholesterol transport pathway genes), five environmental (E) factors (selected from 10), and G x G, E x E, and G x E interactions in explaining population variance of blood lipid concentrations. Total cholesterol, triglycerides, and high density lipoprotein (HDL) cholesterol were measured, and low density lipoprotein (LDL) cholesterol and HDL cholesterol/LDL cholesterol ratio were calculated in a population-based random sample of 1,543 men and women in Geneva, Switzerland, aged 35-74 years in 1999-2001. Explained variances (R2) for HDL cholesterol/LDL cholesterol ratio, HDL cholesterol, and LDL cholesterol, respectively, were 34%, 33%, and 19%, decomposed into main effects of G (6%, 4%, and 5%) and E (25%, 28%, and 11%), with just 3%, 2%, and 3% due to G x G, E x E, and G x E interactions, respectively.

Population-based study of SR-BI genetic variation and lipid profile.

The variability of the Class B Type I Scavenger Receptor (SR-BI) gene in human populations and the relation of its variants to blood lipids was investigated in a random sample of 1756 untreated adult residents of Geneva, Switzerland, during 1999-2000. A three-step study approach yielded the following results: (1) resequencing the gene's exons and flanking regions in 95 subjects identified four common single nucleotide polymorphisms (SNPs with rare allele frequency >3%); (2) association study of the four common SNPs in subjects with extreme HDL-cholesterol (HDL-C) and LDL-C phenotypes (186 "atherogenic cases" and 185 "non-atherogenic controls") showed that the synonymous exon 8 C-T (allelic frequency 48%) polymorphism, A350A, was associated with atheroprotection in men (odds ratios (OR) = 0.36, 95% confidence intervals (CI) = 0.

Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors.

This study explored the genetic basis of the combination of extreme blood levels of HDL-C and LDL-C, a well-studied endophenotype for CVD, which has several attractive features as a target for genetic analysis: (1) the trait is moderately heritable; (2) non-genetic risk factors account for a significant but still limited portion of the phenotypic variance; (3) it is known to be moderated by a number of gene products. We exhaustively surveyed 11 candidate genes for allelic variation in a random population-based sample characterized for known CVD risk factors and blood lipid profiles. With the goal of generating specific etiological hypotheses, we compared two groups of subjects with extreme lipid phenotypes, from the same source population, using a case-control design.

Association between lipoprotein lipase (LPL) gene and blood lipids: a common variant for a common trait?

S447X, a serine substitution by a stop codon on base 99 of exon 9 of the lipoprotein lipase (LPL) gene, has beneficial effects on blood lipids. Other LPL alleles are associated with lipid levels, but whether one of these variants predominates remains elusive. We performed a systematic survey to identify single-nucleotide polymorphisms (SNPs) in all 10 LPL exons and flanking regions by resequencing the gene in 95 subjects.