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Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

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 ADH1B·1/1 genotype compared to 7.5 drinks (95% CI: 6.4–8.7) among men with the ADH1B·1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7–5.7) among men with the ADH1B·1/1 genotype compared to men with the ADH1B·1/2 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 ADH1C·1/2 genotype and 1.4 (95% CI: 1.0–1.9) among men with the ADH1B·2/2 genotype, compared with men with the ADH1C·1/1 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 ADH1B·1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

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Abbreviations

ADH:

alcohol dehydrogenase

bMAST:

brief Michigan Alcoholism Screening Test

OR:

odds ratio

PAR:

population attributable risk

Ref:

Reference group

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Acknowledgements

This work was supported by grants from the Danish Graduate School of Public Health, the Health Insurance Foundation, the Ministry of the Interior and Health and the Danish National Board of Health and The Danish Heart Foundation, The Danish Medical Research Council, The Copenhagen County Research Foundation and Chief Physician Johan Boserup and Lise Boserups Foundation. We thank the participants of the Copenhagen City Heart Studies.

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Correspondence to Janne Schurmann Tolstrup.

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Tolstrup, J., Nordestgaard, B., Rasmussen, S. et al. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes. Pharmacogenomics J 8, 220–227 (2008). https://doi.org/10.1038/sj.tpj.6500471

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