Alcohol Metabolism in Asian-American Men with Genetic Polymorphisms of Aldehyde Dehydrogenase

  1. Tamara L. Wall, PhD;
  2. Charles M. Peterson, MD;
  3. Karen P. Peterson, PhD;
  4. Mona L. Johnson, BA;
  5. Holly R. Thomasson, MD, PhD;
  6. Maury Cole, BA; and
  7. Cindy L. Ehlers, PhD
  1. From the University of California. San Diego, San Diego, California; The Scripps Research Institute, La Jolla, California; Sansum Medical Research Foundation, Santa Barbara, California; and Eli Lilly and Co., Indianapolis, Indiana. Acknowledgments: The authors thank Evie Phillips, Catherine Rowell, Daisy Zeng, Dr. T.-K. Li, and Dr. Marc Schuckit. Grant Support: By grants AA-00098, AA-00155, AA-06420, AA-07611, AA-11257, and RR-00833 from the National Institutes of Health. Requests for Reprints: Tamara L. Wall, PhD, University of California, San Diego, Department of Psychiatry, San Diego Veterans Affairs Medical Center (116B), 3350 La Jolla Village Drive, San Diego, CA 92161. Current Author Addresses: Dr. Wall and Ms. Johnson: University of California, San Diego, Department of Psychiatry, San Diego Veterans Affairs Medical Center (116B), 3350 La Jolla Village Drive, San Diego, CA 92161.

    Abstract

    Background: About half of certain Asians have a deficiency of the low-Km aldehyde dehydrogenase (ALDH2) isoenzyme. This deficiency results from inheritance of mutant ALDH2*2 allele.

    Objective: To determine whether Asian Americans with ALDH2*2 alleles differ from Asian Americans without this mutation in terms of blood levels of alcohol and acetaldehyde after ingestion of a moderate amount of alcohol.

    Design: Double-blind, crossover study.

    Setting: Private research institute.

    Participants: 35 healthy Asian-American men. Three men who became ill after alcohol ingestion and one who had outlying data were excluded.

    Intervention: Alcoholic beverage, containing 0.56 g of alcohol per kg of body weight, or placebo beverage, containing 3 mL of alcohol, given orally on separate occasions.

    Measurements: Blood levels of alcohol and acetaldehyde measured before and several times after ingestion of the alcoholic or placebo beverage.

    Results: Participants with ALDH2*2 alleles had significantly higher blood acetaldehyde levels after ingesting alcoholic and placebo beverages than did participants with ALDH2*1 alleles, despite similar blood alcohol concentrations.

    Conclusions: Blood acetaldehyde levels rather than blood alcohol concentration may mediate enhanced alcohol sensitivity among Asians with ALDH2*2 alleles.

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