title: CETP TaqIB genotype modifies the association between alcohol and coronary heart disease: the INTERGENE case-control study.
abstract: Alcohol consumption at moderate levels has been associated with decreased risk of coronary heart disease (CHD). However, the cardio-protective effect of alcohol may be restricted to subjects with a particular genotype of the cholesteryl ester transfer protein (CETP) polymorphism. There is evidence for this from one study in men, but the finding has not been confirmed since. The present study specifically re-examines the potential modification of the association between alcohol consumption and CHD by the CETP TaqIB (rs708272) polymorphism in a sample including both men and women. The INTERGENE case-control study consists of 618 patients with CHD and 2921 control subjects, of whom 19% were homozygous for the CETP TaqIB B2 allele. Alcohol consumption was categorized into sex-specific tertiles of ethanol intake, with non-drinkers constituting a separate category. Logistic regression was used to determine the association between CHD with genotype, ethanol intake, and their interaction. Participants with intermediate ethanol intake (2nd tertile) had lower risk of CHD than those with low ethanol intake (odds ratio [OR] = 0.65; 95% confidence interval [CI] 0.50-0.85). The strongest protective association was seen in the CETP TaqIB B2 homozygotes for intermediate vs. low ethanol intake (odds ratio OR = 0.21; 95% CI 0.10-0.44). The interaction between ethanol intake and genotype was statistically significant (p = 0.008), and of similar size in men and women though significant only in men (p = 0.01). The effect modification could not be explained by differences in lifestyle, socioeconomics, or alcohol-related biological variables such as HDL-cholesterol. Our study is the first to replicate previous findings of an effect modification in men. It gives only suggestive results for women, possibly due to the small number of female cases (n = 165). The prevented fraction for the favorable combination of genotype and alcohol consumption is about 6%, a value suggesting that the cardio-protective effect of moderate alcohol consumption applies only to a small segment of the general population.
authors.affiliation: Department of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden. Electronic address: kirsten.mehlig@gu.se.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Mehlig
authors.affiliation: Department of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Strandhagen
authors.affiliation: Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, 413 45 Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 413 45 Gothenburg, Sweden.
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Svensson
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 413 45 Gothenburg, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Rosengren
authors.affiliation: Section of Occupational and Environmental Medicine, Institute of Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Torén
authors.affiliation: Department of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden; Department of Biostatistics, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway.
authors.forename: Dag S
authors.initials: DS
authors.lastname: Thelle
authors.affiliation: Department of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Lauren
authors.initials: L
authors.lastname: Lissner
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects*; D016022:Case-Control Studies; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D003327:Coronary Disease / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins
keywords: Alcohol; CETP polymorphism; Coronary heart disease; Gene-environment interaction; Prevented fraction