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.