GeneticsLandmark
Landmark ECTIM study is the first to show alcohol intake determines whether the CETP B2 allele protects against heart attack (J Clin Invest 1995)
Original title: Alcohol intake modulates the effect of a polymorphism of the cholesteryl ester transfer protein gene on plasma high density lipoprotein and the risk of myocardial infarction
This large ECTIM case-control study of men aged 25-64 investigated the CETP TaqIB polymorphism (B1 60%, B2 40%) in relation to lipid variables and myocardial infarction (MI) risk. No association was found with LDL or VLDL-related lipid variables, but B2 carriers had reduced plasma CETP (P less than 0.0001) and increased HDL-cholesterol and related HDL variables (P less than 0.0001), effects that were independent of each other, suggesting at least two functional variants linked to B2 that a coding-sequence search failed to identify. The effect of B2 on HDL-cholesterol was absent in subjects drinking less than 25 g/day of alcohol but increased proportionally with higher alcohol consumption (interaction P less than 0.0001), an interaction not seen for plasma CETP. The odds ratio for MI in B2 homozygotes fell from 1.0 in nondrinkers to 0.34 in those drinking 75 g/day or more. The authors report this as the first demonstration of a gene-environment interaction affecting both HDL-cholesterol and coronary heart disease risk.
Original abstract
A polymorphism of the CETP gene (CETP/TaqIB) with two alleles B1 (60%) and B2 (40%) has been investigated in relation to lipid variables and the risk of myocardial infarction in a large case-control study (ECTIM) of men aged 25-64. No association was observed between the polymorphism and LDL or VLDL related lipid variables. Conversely, B2 carriers had reduced levels of plasma CETP (P < 0.0001) and increased levels of HDL cholesterol (P < 0.0001) and of other HDL related lipid variables. The effects of the polymorphism on plasma CETP and HDL cholesterol were independent, suggesting the presence of at least two functional variants linked to B2. A search for these variants on the coding sequence of the CETP gene failed to identify them. The effect of B2 on plasma HDL cholesterol was absent in subjects drinking < 25 grams/d of alcohol but increased commensurably, with higher values of alcohol consumption (interaction: P < 0.0001). A similar interaction was not observed for plasma CETP. The odds-ratio for myocardial infarction of B2 homozygotes decreased from 1.0 in nondrinkers to 0.34 in those drinking 75 grams/d or more. These results provide the first demonstration of a gene-environment interaction affecting HDL cholesterol levels and coronary heart disease risk.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.