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Specific genetic factors modify the reduction in heart disease risk from alcohol consumption

It has long been known that genetic and other environmental factors modify the association between alcohol consumption and a variety of diseases, especially coronary heart disease (CHD). Foremost among these modifying factors are genes that affect alcohol metabolism, age (effects seen only in older individuals), and drinking patterns (regular moderate versus binge drinking). Also, certain cholesteryl ester transfer protein (CETP TaqIB) polymorphisms, that relate to HDL-cholesterol activity, may interact with alcohol consumption for their effects on the risk of CHD. In the present study, the investigators have carried out a population-based case-control study among subjects in southwest Sweden to determine if there was an interaction between CETP genotypes and alcohol consumption for its effects on the risk of CHD. The authors conclude that a significant reduction in the risk of CHD from moderate drinking was seen only among the 18.6% of their subjects who had a particular CETP polymorphism.

Forum members considered this to be an interesting paper, but had some questions about the selection of cases, as they included not only new cases of CHD but subjects “who had an exacerbation of previously diagnosed coronary heart disease;” this makes it somewhat difficult to compare their results with other papers. Further, despite a large number of potential “control” subjects from their base population, the controls chosen were considerably younger than the cases and had different medical histories. While they adjusted for some of these factors in their analysis, residual confounding remains possible.

The major concern of Forum members was the broad conclusion of the authors (that only a small proportion of the population will show any cardio-protective effects of moderate drinking) based on such a small number of subjects. For example, among their “intermediate” category of drinkers with the supposedly “protective” CETP polymorphism, there were only 13 cases of CHD. Further, a number of previous large studies have had quite conflicting results regarding the effects of CETP polymorphisms on the alcohol-CHD association. While this paper adds information on one (of many) factors that affect the association between alcohol consumption and CHD, larger studies in different populations will be needed to determine the overall importance of this particular genetic polymorphism. Reference: Mehlig K, Strandhagen E, Svensson P-A, Rosengren A, Torén K, Thelle DS, Lissner L. CETP TaqIB genotype modifies the association between alcohol and coronary heart disease: The INTERGENE case-control study. Alcohol 2014;48:695e700.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.
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