Alcohol Consumption and Type 2 Diabetes

Influence of Genetic Variation in Alcohol Dehydrogenase

  1. Joline W.J. Beulens123,
  2. Eric B. Rimm145,
  3. Henk F.J. Hendriks3,
  4. Frank B. Hu145,
  5. JoAnn E. Manson456,
  6. David J. Hunter457 and
  7. Kenneth J. Mukamal18
  1. 1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
  2. 2Department of Human Nutrition, Wageningen University, Wageningen, the Netherlands
  3. 3Department of Physiological Sciences, Netherlands Organization for Applied Scientific Research Quality of Life, Zeist, the Netherlands
  4. 4Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
  5. 5Channing Laboratory, Harvard Medical School, Boston, Massachusetts
  6. 6Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
  7. 7Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts
  8. 8Department of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  1. Address correspondence and reprint requests to Joline W.J. Beulens, PhD, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, Netherlands. E-mail: j.beulens{at}umcutrecht.nl

Abstract

OBJECTIVE— We sought 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 1,000 control subjects from the Nurses’ Health Study and 383 men with incident diabetes and 382 control subjects from the Health Professionals Follow-Up Study, we determined associations between the ADH1C polymorphism, alcohol consumption, and diabetes risk.

RESULTS— Moderate to heavy 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 (1.08 [0.67–1.75]). ADH1C genotype modified the relation between alcohol consumption and diabetes for women (Pinteraction = 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 (Ptrend = 0.002). These results were not significant among men. Results were similar in pooled analyses (Pinteraction = 0.02) with ORs for diabetes among moderate drinkers of 0.44 (95% CI 0.21–0.94) in ADH1C*1 homozygotes, 0.65 (0.39–1.06) for heterozygotes, and 0.78 (0.50–1.22) for ADH1C*2 homozygotes compared with those for ADH1C*1 homozygote abstainers (Ptrend = 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 heavy 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.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 11 June 2007. DOI: 10.2337/db07-0181.

  • J.W.J.B. is currently affiliated with Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.

  • Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-0181.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted May 25, 2007.
    • Received February 9, 2007.
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  1. Published online before print June 11, 2007, doi: 10.2337/db07-0181 Diabetes September 2007 vol. 56 no. 9 2388-2394
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