Genetics
Ten CETP polymorphisms mapped in 568 heart-attack patients reveal alcohol-dependent effects on HDL cholesterol (Genet Epidemiol 2000)
Original title: Extensive association analysis between the CETP gene and coronary heart disease phenotypes reveals several putative functional polymorphisms and gene-environment interaction
An association analysis of ten CETP gene polymorphisms, three newly identified in regulatory regions, was performed in 568 myocardial infarction patients and 668 controls. The Ile405Val and G(+524)T polymorphisms were almost completely concordant and associated with plasma CETP mass (P less than 0.001), while polymorphisms at -629 in the promoter, intron1 (Taq1B), and intron7 were concordant and associated with both CETP mass and HDL-cholesterol (P less than 0.0001), an association absent in teetotalers and strengthening with alcohol intake. Heavy drinkers homozygous for the -628 A allele had a reduced infarction risk (odds ratio 0. 33, P less than 0.02), and subjects homozygous for 451Arg and heterozygous for 373Pro had lower HDL-cholesterol, an effect that grew with alcohol consumption, together indicating the CETP gene carries several functional polymorphisms whose effects on HDL depend on gene-environment interaction and mutual confounding by linkage disequilibrium.
Original abstract
An extensive association analysis of a candidate gene for coronary heart disease, Cholesteryl Ester Transfer Protein (CETP) gene, was performed. Ten polymorphisms, out of which three were newly identified in regulatory regions, were investigated for association with myocardial infarction (MI) and 2 MI endophenotypes (CETP mass and HDL-cholesterol level) in 568 MI patients and 668 controls. The polymorphisms affecting codon 405 (Ile(405)Val) and the nucleotide 524 downstream from the stop codon (G(+524)T) were almost completely concordant and associated with plasma CETP mass (P < 0.001). The polymorphisms -629 (located in promoter), intron1 (Taq1B) and intron7 were almost completely concordant and associated with plasma CETP mass (P < 0.0001) and HDL-cholesterol levels (P < 0.0001). This latter association was not found in teetotalers and increased with the quantity of alcohol consumed. Heavy drinkers (>75g/day) homozygous for the (-628)A allele had a reduced risk of MI (OR = 0. 33, P < 0.02). Subjects both homozygous for (451)Arg and heterozygous for (373)Pro had decreased plasma HDL-cholesterol levels and this effect increased with alcohol consumption. The results illustrate the complexity of polymorphism-phenotype associations. They suggest that the CETP gene may carry several functional polymorphisms. Observed interactions between alcohol consumption and polymorphisms associated with HDL-cholesterol level constitute concrete examples of gene-environment interactions. Furthermore, the pattern of association between HDL-cholesterol levels and the polymorphisms at codons 373 and 451 illustrated how two polymorphisms may be confounders (in the usual epidemiological sense) one for the other: their marginal effects are neutralized because of linkage disequilibrium and thus are not detectable by standard univariate association analysis.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.