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

Tamara L. Wall, PhD; Charles M. Peterson, MD; Karen P. Peterson, PhD; Mona L. Johnson, BA; Holly R. Thomasson, MD, PhD; Maury Cole, BA; and Cindy L. Ehlers, PhD
[+] Article, Author, and Disclosure Information

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.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;127(5):376-379. doi:10.7326/0003-4819-127-5-199709010-00007
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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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Figure 1.
Mean (±SD) blood levels of alcohol and acetaldehyde before and after ingestion of a placebo beverage containing 3 mL of 95% alcohol and an alcoholic beverage (0.nnP

56 g of alcohol per kg of body weight) in Asian-American men with ALDH2*1/2*1 genotype ( = 20) and ALDH2*1/2*2 genotype ( = 11). Blood alcohol concentrations measured after administration of placebo were not detectable and thus are not shown. Significant interactions between ALDH2 genotype and time were followed by post hoc tests with Bonferroni corrections. An asterisk indicates significant differences between the ALDH2 genotype groups ( < 0.006).

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