ALDH2, ADH1B, and ADH1C genotypes in Asians: a literature review

Alcohol Research & Health,  Wntr, 2007  by Mimy Y. Eng,  Susan E. Luczak,  Tamara L. Wall

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Variants of three genes encoding alcohol-metabolizing enzymes, the aldehyde dehydrogenase gene ALDH2 and the alcohol dehydrogenase genes ADH1B and ADH1C, have been associated with reduced rates of alcohol dependence. The genotype prevalence of these genes varies in general samples of different Asian ethnic groups. The ALDH2*2 allele appears to be most prevalent in Chinese-American, Han Chinese and Taiwanese, Japanese, and Korean samples. Much lower rates have been reported in Thais, Filipinos, Indians, and Chinese and Taiwanese aborigines. ADH1B*2 is highly prevalent among Asians, with the exception of Indians. ADH1C*1 also is highly prevalent in Asians, but has only been examined in a few studies of Chinese and Korean samples. KEY WORDS: Alcohol dependence; ethanol metabolism; ethanol-to-acetaldehyde metabolism; alcohol dehydrogenase (ADH); aldehyde dehydrogenase (ALDH); acetaldehyde; ALDH2; ADH1B; ADH1C; risk factors; protective factors; genetic factors; ethnic groups; Asians; Chinese; Filipino; Indian; Japanese; Korean; Malaysian; Thai

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People of Asian descent, as a whole, have lower rates of alcohol dependence compared with other ethnic groups (Grant et al. 2004). Within Asians, however, rates of alcohol dependence differ across ethnic subgroups. For example, relatively high rates of alcohol dependence have been found among Koreans and Korean Americans, whereas relatively low rates have been found in Chinese and Chinese Americans (Helzer et al. 1990; Luczak et al. 2004). Prevalence rates of alleles of genes encoding alcohol-metabolizing enzymes vary across Asian ethnicities (e.g., Goedde et al. 1992). This may in part account for some of the ethnic differences in rates of alcohol involvement. The purpose of this article is to review genotype (1) prevalence rates of three genes, the aldehyde dehydrogenase gene ALDH2 and the alcohol dehydrogenase genes ADH1B and ADHIC. (2)

These three genes code for isoenzymes that metabolize alcohol into acetaldehyde (ADH1B and ADH1C) and acetaldehyde into acetate (ALDH2). The common forms of these alleles are ADH1B*1, ADH1C*2, and ALDH2*1. The variant forms of the alleles (ADH1B*2, ADH1C*1, and ALDH2*2) are hypothesized to alter conversion rates during alcohol metabolism and lead to an excess buildup of acetaldehyde (see Eriksson 2001). The excess acetaldehyde is thought to lead to heightened responses to alcohol and thereby reduce heavy alcohol use, associated problems, and the development of alcohol use disorders (see Wall et al. 2005 for further details). A meta-analysis of 15 Asian (Chinese, Japanese, Korean, and Thai) studies with data from over 4,500 alcohol-dependent and control subjects collected between 1979 and 2004 found possession of one variant ALDH2*2 allele was associated with a fivefold reduction in alcohol is dependence and possession of two ALDH2*2 alleles was associated with a nine-fold reduction (Luczak et al. 2006). (3) In Asians with no ALDH2*2 alleles, possession of one variant ADH1B*2 allele was associated with a four-fold reduction in alcohol dependence and possession of two ADHIB*2 alleles was associated with a five-fold reduction (Luczak et al. 2006). ADH1C*1 also has been related to protection against alcohol dependence, but this association has been attributed to the ADH1C gene being in close proximity to the ADH1B gene on the chromosome so that the genotypes are correlated (Osier et al. 1999).

Determining how frequently certain genotypes occur in different populations is useful for behavioral genetics research. It is important to establish the prevalence rates of these genotypes in various ethnic groups to determine their unique contribution to alcohol involvement within each ethnicity. To achieve this goal for Asian populations, an extensive literature review of studies determining the prevalence of the ALDH2, ADH1B, and ADH1C genotypes in various Asian ethnic groups was performed, as described in the following sections.

PREVALENCE OF ALDH2, ADH1B, AND ADH1C GENOTYPES IN ASIAN POPULATIONS

Study Design

To identify studies eligible for this analysis, the authors of this article surveyed the Medline literature database using the National Library of Medicine's PubMed (January 1966 to April 2006) online search engine. The search first was conducted using the keywords "(aldehyde dehydrogenase OR ALDH) AND Asian;" then, additional searches were conducted by replacing "Asian" with specific Asian ethnicities (i.e., Chinese, Filipino, Indian, Japanese, Korean, Malaysian, and Thai). The series of searches then was repeated using the keywords "(alcohol dehydrogenase OR ADH)." The retrieved abstracts were read to identify studies that reported prevalence rates of the various ALDH2, ADH1B, and ADH1C genotypes in general samples of the different ethnic groups. The studies thus identified were read in their entirety to assess whether they were appropriate for including in this analysis. Studies that reported only allele frequencies instead of genotypes, compared treatment samples with control groups, or selected samples based on specific alcohol-related medical conditions (e.g., cirrhosis or head and neck cancers) were excluded. All references cited in the appropriate articles also were reviewed to identify additional relevant publications.