Original Article

The Pharmacogenomics Journal (2008) 8, 220–227; doi:10.1038/sj.tpj.6500471; published online 9 October 2007

Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

Janne Schurmann Tolstrup1,2, Børge Grønne Nordestgaard2,3, Søren Rasmussen1, Anne Tybjærg-Hansen4 and Morten Grønbæk1,3

  1. 1Center for Alcohol Research, National Institute of Public Health, Copenhagen, Denmark
  2. 2Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark
  3. 3The Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark
  4. 4Department of Clinical Biochemistry, Copenhagen University Hospital, Copenhagen, Denmark

Correspondence: Dr JS Tolstrup, Center for Alcohol Research, National Institute for Public Health, Oster Farimagsgade 5a, Copenhagen, 1399 Denmark. E-mail: jst@niph.dk

Received 18 March 2007; Revised 4 June 2007; Accepted 13 June 2007; Published online 9 October 2007.

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Abstract

Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1–11) among men with the ADH1Bdot1/1 genotype compared to 7.5 drinks (95% CI: 6.4–8.7) among men with the ADH1Bdot1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7–5.7) among men with the ADH1Bdot1/1 genotype compared to men with the ADH1Bdot1/2 genotype. Furthermore, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1–1.8) among men with the ADH1Cdot1/2 genotype and 1.4 (95% CI: 1.0–1.9) among men with the ADH1Bdot2/2 genotype, compared with men with the ADH1Cdot1/1 genotype. Results for ADH1B and ADH1C genotypes among men and women were similar. Finally, because slow ADH1B alcohol degradation is found in more than 90% of the white population compared to less than 10% of East Asians, the population attributable risk of heavy drinking and alcoholism by ADH1Bdot1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

Keywords:

genetic association study, alcoholism, population-based study, alcohol, alcohol dehydrogenase, acetaldehyde

Abbreviations:

ADH, alcohol dehydrogenase; bMAST, brief Michigan Alcoholism Screening Test; OR, odds ratio; PAR, population attributable risk; Ref, Reference group

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