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Interaction Effects of High-Density Lipoprotein Metabolism Gene Variation and Alcohol Consumption on Coronary Heart Disease Risk: The Atherosclerosis Risk in Communities Study

Kelly Volcik, Christie M. Ballantyne, Henry J. Pownall, A. Richey Sharrett, Eric Boerwinkle

Objective: Light to moderate alcohol consumption has been widely established to be protective against coronary heart disease (CHD), whereas heavy alcohol consumption has been shown to have a potential detrimental effect. The reduction in risk of CHD associated with light and moderate alcohol intake is generally attributed to the beneficial effects of alcohol on high-density lipoprotein (HDL) cholesterol levels. Previous research in the Atherosclerosis Risk in Communities (ARIC) study showed all levels of alcohol consumption to be protective against CHD in whites but to be associated with an increased risk of CHD in black men. We investigated the ARIC cohort to determine whether risk of incident CHD is influenced by an interaction effect between alcohol intake and genetic variation involved in the regulation of HDL cholesterol. Genes of interest included cholesterol ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic lipase (HL), and paraoxonase-1 (PON1). Method: Participants were selected from the ARIC study, a prospective investigation of atherosclerosis and its clinical sequelae, involving 15,792 individuals, ages 4564 years at recruitment (19871989). Incident CHD was identified through annual telephone calls and hospital and death certificate surveillance. Because of ethnic differences in the alcohol-CHD relationship observed in the ARIC cohort and pattern of alcohol consumption differences, statistical analyses were evaluated separately for each race-gender stratum (white men/women, black men/women). Results: Genotype modified the relationship between heavy drinking and CHD risk but did not modify this relationship for light or moderate drinking. Interaction analyses were significant for heavy alcohol intake and PON1 genotype (p .02) in black men, with a suggested interaction for heavy alcohol intake and CETP genotype (p .06) in black men. Heavy drinking was associated with an increased risk for CHD in black men with the PON1 QQ and CETP GG genotypes (PON1 hazard rate ratio [HRR] 17.3, 95% confidence interval [CI]: 1.76-170.2; CETP HRR 2.23, 95% CI: 1.01-4.91). Conclusions: Results from the current study suggest that interaction effects between alcohol consumption and HDL cholesterol metabolism gene variation influence the risk of incident CHD in black men. Additional studies are warranted to confirm these findings. (J. Stud. Alcohol Drugs 68: 485-492, 2007)