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Research Summary

Inherited Differences in Metabolism Influence Risk of Alcohol Dependence

About 50% of a person's risk for alcohol dependence is determined by genetics. Emerging research suggests that this propensity toward dependence may result from inherited differences in metabolism.

  • Chai and colleagues genotyped 24 Korean men with the early-onset, familial form of alcoholism (Type II), 48 with late-onset alcoholism (Type I), and 38 healthy controls. They found that
    • high-active forms of the alcohol dehydrogenases ADH2 and ADH3, which convert ethanol to acetate and acetaldehyde (a toxin that causes flushing and other unpleasant symptoms) were significantly more common in healthy controls and men with late-onset alcoholism than in men with early-onset familial alcoholism;
    • active forms of aldehyde dehydrogenase ALDH2, which clears the toxin acetaldehyde, were significantly less common in healthy controls than in men with either type of alcoholism.
  • Guindalini et al genotyped 92 patients with alcoholism and 92 healthy subjects, and reported that
    • the healthy subjects were significantly more likely to have 2 alleles associated with more active (and protective) forms of the alcohol dehydrogenase ADH4 than were patients with alcoholism.

Comments:

A metabolic predisposition to produce and accumulate acetaldehyde is protective against alcohol dependence, and these studies have isolated specific genetic targets. After further verification in larger samples, these findings hold great promise for genetic testing and targeted prevention, medication development, and even genetic therapy.

Peter D. Friedmann, MD, MPH

Reference:

Chai YG, Oh DY, Chung EK, et al. Alcohol and aldehyde dehydrogenase polymorphisms in men with type I and type II alcoholism. Am J Psychiatry. 2005;162(5):1003-1005.

Guindalini C, Scivoletto S, Ferreira RGM, et al. Association of genetic variants of alcohol dehydrogenase 4 with alcohol dependence in Brazilian patients. Am J Psychiatry. 2005;162(5):1005-1007.


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