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Alcohol consumption and type 2 diabetes: influence of genetic variation in alcohol dehydrogenase

¹Department of Nutrition (JWB, EBR, FBH, KJM), Department of Epidemiology (EBR, FBH, JEM, DJH), Program in Molecular and Genetic Epidemiology (DJH), Harvard School of Public Health, Boston, MA; Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands (JWB); Department of Physiological Sciences, TNO Quality of Life, Zeist, The Netherlands (JWB, HFH); Channing Laboratory, Harvard Medical School (EBR, FBH, JEM, DJH); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital (JEM), Boston, MA; Department of General Medicine and Primary Care, Beth Israel Deaconess Medical Center (KJM), Boston, MA

Correspondence: J.beulens{at}umcutrecht.nl

Objective:To investigate whether a polymorphism in the alcohol dehydrogenase 1c (ADH1C) gene modifies the association between alcohol consumption and type 2 diabetes.

Research Design and Methods:In nested case-control studies of 640 women with incident diabetes and 1000 controls from the Nurses' Health Study, and 383 men with incident diabetes and 382 controls from the Health Professionals Follow-up Study, we determined associations between the ADH1C polymorphism, alcohol consumption and diabetes risk.

Results:Moderate to heavier alcohol consumption (>5 g/day for women and >10 g/day for men) was associated with a decreased risk of diabetes among women (odds ratio (OR): 0.45; 95%-CI: 0.33-0.63), but not men (OR: 1.08; 0.67-1.75). ADH1C genotype modified the relation between alcohol consumption and diabetes for women (p_interaction= 0.02). The number of ADH1C*2 alleles, related to a slower rate of ethanol oxidation, attenuated the lower risk of diabetes among women consuming 5 g alcohol/day (p_trend= 0.002). These results were not significant among men. Results were similar in pooled analyses (p_interaction= 0.02) with OR's for diabetes among moderate drinkers of 0.44 (0.21-0.94) among ADH1C*1 homozygotes, 0.65 (0.39-1.06) for heterozygotes and 0.78 (0.50-1.22) for ADH1C*2 homozygotes compared to ADH1C*1 homozygote abstainers (p_trend= 0.02).

Conclusions: ADH1C genotype modifies the association between alcohol consumption and diabetes. The ADH1C*2 allele, related to a slower oxidation rate, attenuates the lower diabetes risk among moderate to heavier drinkers. This suggests that the association between alcohol consumption and diabetes may be causal but mediated by downstream metabolites such as acetate rather than ethanol itself.

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