|
ALDH2, ADH1B, and ADH1C Genotypes in Asians: A Literature Review
Mimy Y. Eng, Ph.D.; Susan E. Luczak, Ph.D.; and Tamara L. Wall, Ph.D.
Mimy Y. Eng, Ph.D., is a postdoctoral fellow in the Department of Psychiatry, University of California, San Diego, and the Veterans Medical Research Foundation, San Diego, California.
Susan E. Luczak, Ph.D., is an assistant research professor in the Department of Psychology, University of Southern California, Los Angeles, California, and an assistant adjunct professor in the Department of Psychiatry, University of California, San Diego, California.
Tamara L. Wall, Ph.D., is a professor in the Department of Psychiatry, University of California, and associate chief of the Psychology Service, Veterans Affairs San Diego Healthcare System, San Diego, California, and a research scientist in the Veterans Medical Research Foundation, San Diego, California.
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
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 genotype1 prevalence rates of three genes, the aldehyde dehydrogenase gene ALDH2 and the alcohol dehydrogenase genes ADH1B and ADH1C.2 (1Every person possesses two copies of each allele; these two alleles make up the genotype.) (2ADH1B and ADH1C were formerly called ADH2 and ADH3, respectively [for more information, see the accompanying article by Edenberg].)
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 five-fold reduction in alcohol is dependence and possession of two ALDH2*2 alleles was associated with a nine-fold reduction (Luczak et al. 2006).3 (3If a person has two copies of the same allele, the person is called homozygous for that allele; if the two copies are of different alleles, the person is called heterozygous.) 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 ADH1B*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.
Despite the stringent criteria for the selection of studies to be included, the following caveats should be noted:
Some samples included in the analysis may not be entirely random because participants were screened for certain medical disorders (e.g., diabetes, heart conditions, and stroke) that have been related to alcohol in addition to other factors.
Samples with allele distributions that do not meet Hardy-Weinberg equilibrium4 (which are marked in the table summarizing the results) should be viewed with caution because the genotype distribution in these studies is not consistent with the expected distribution for a general sample. (4 Hardy-Weinberg equilibrium is the stable frequency distribution of genotypes, as measured by the proportion of the alleles that result as a consequence of random mating. )
Results of the Analysis
Distribution of ALDH2 Genotypes.
The ALDH2*2 allele is thought to occur exclusively in Asians; however, its prevalence varies across Asian ethnicities (see Table 1). Five studies determined the ALDH2 genotype in Han Chinese and Taiwanese people.5 (5 The Han are the main ethnic group found in the People’s Republic of China and Taiwan.) In these studies, 20 to 47 percent of the participants were heterozygous and 1 to 8 percent were homozygous for ALDH2*2 (Goedde et al. 1992; Luo et al. 2001, 2005; Novoradovsky et al. 1995; Shen et al. 1997). Overall, approximately one-third of the Han Chinese possessed at least one ALDH2*2 allele. The prevalence of the ALDH2*2 allele was particularly high in one study of Han Taiwanese and two studies of Chinese Americans, with about half of these samples possessing at least one ALDH2*2 allele, including 7 to 8 percent who were homozygous for ALDH2*2 (Hendershot et al. 2005; Luczak et al. 2004; Novoradovsky et al. 1995). The large variation in prevalence rates found among Han Chinese and Taiwanese samples might be explained by the different geographic locations from which the samples were obtained. The sample with the highest prevalence was from Taiwan, where 55 percent of participants possessed at least one ALDH2 allele (Novoradovsky et al. 1995). Conversely, the samples with the lowest prevalence were from central and northern China, where 22 percent of participants possessed at least one ALDH2*2 allele (Luo et al. 2001; Shen et al. 1997). For the studies with intermediate prevalence rates (i.e., 30 to 32 percent), the samples were from southwest China (Luo et al. 2005) or their location was not reported (Goedde et al. 1992).
The ALDH2*2 allele was less commonly found in aboriginal Chinese and Taiwanese samples (e.g., Ami, Atayal, Bunun, Elunchan, Mongolian, and Paiwan), with 2 to 12 percent of study participants being heterozygous and only 0.3 percent (i.e., 2 of 585 people analyzed) being homozygous for ALDH2*2 (Chen et al. 1997; Shen et al. 1997; Thomasson et al. 1994).
Data from 10 Japanese studies indicated that 41 to 52 percent of Japanese possessed at least one ALDH2*2 allele, including 1 to 8 percent who were homozygous for ALDH2*2 (Amamoto et al. 2002; Goedde et al. 1992; Higuchi et al. 1996; Saito et al. 2003; Sun et al. 1999; Takeshita and Morimoto 1999: Takeshita et al. 1994; Tanaka et al. 1997; Yamada et al. 2002; Yokoyama et al. 2005). Somewhat higher rates were reported in one small Japanese study (N = 15), in which 66 percent of the participants possessed at least one ALDH2*2 allele, including 13 percent who were homozygous for ALDH2*2 (Shibuya et al. 1989).
Five studies of Korean, Korean-American, and Korean-Chinese samples found that approximately one-third (29 to 37 percent) of Koreans had at least one ALDH2*2 allele, including 2 to 3 percent who were homozygous for ALDH2*2 (Goedde et al. 1992; Hendershot et al. 2005; Lee et al. 1997; Luczak et al. 2004; Shen et al. 1997). Finally, ALDH2*2 was much less common among other Asian ethnicities, including Filipinos, Indians, Malays, Siberian Yakuts, and Thais, than in Chinese, Japanese, and Korean samples, with 0 to 10 percent of study participants possessing at least one ALDH2*2 allele (Goedde et al. 1992; Novoradovsky et al. 1995). Taken together, all the studies reviewed here demonstrate great diversity among Asian ethnic groups in the prevalence of heterozygosity or homozygosity for ALDH2*2.
Distribution of ADH1B Genotypes. The ADH1B*2 allele was highly prevalent in Asian ethnic groups, particularly in northeast Asians (i.e., Chinese, Japanese, and Koreans) (see Table 1). Among the Han Chinese and Taiwanese and the Chinese Americans, 84 to 92 percent possessed at least one ADH1B*2 allele, including 40 to 60 percent who were homozygous for ADH1B*2 (Chao et al. 1987; Goedde et al. 1992; Lee et al. 1989; Luczak et al. 2004; Shen et al. 1997). Rates of having at least one ADH1B*2 allele were slightly lower in some Chinese and Taiwanese aborigine groups (e.g., 63 percent in Elunchan, 74 percent in Mongolian, and 78 percent in Ami) but were higher in others (e.g., 98 to 100 percent in Atayal, Bunun, and Paiwan) (Chen et al. 1997; Shen et al. 1997; Thomasson et al. 1994).
The ADH1B*2 allele also was commonly found in Japanese people. In 10 studies of Japanese, 81 to 100 percent of participants possessed at least one ADH1B*2 allele, including 34 to 71 percent who were homozygous for the allele (Goedde et al. 1992; Higuchi et al. 1996; Saito et al. 2003; Shibuya et al. 1989; Sun et al. 1999; Suzuki et al. 2004; Takeshita et al. 1996; Tanaka et al. 1997; Yamada et al. 2002; Yin et al. 1984). The results of one of the studies (Yin et al. 1984), in which ADH1B*2 prevalence rates were among the lowest for Japanese and Japanese Americans, however, must be viewed with caution because the distributions were not in Hardy-Weinberg equilibrium.
The prevalence of ADH1B*2 also was high in three Korean samples, with 88 to 96 percent of participants possessing at least one ADH1B*2 allele and 50 to 65 percent possessing two ADH1B*2 alleles (Goedde et al. 1992; Luczak et al. 2004; Shen et al. 1997). Among Filipinos and Malays, more than 80 percent of study participants carried at least one ADH1B*2 allele (Goedde et al. 1992) as well. Intermediate rates were found in Thais (54 percent), and ADH1B*2 was least common in Indians, where only 15 percent possessed at least one copy of the allele (Goedde et al. 1992).
Distribution of ADH1C Genotypes. ADH1C genotypes only have been examined in a few Chinese and Korean samples, but in these samples the ADH1C*1 allele was highly prevalent. In one study of Han Chinese, 97 percent of participants possessed at least one ADH1C*1 allele, including 83 percent who were homozygous (Shen et al. 1997). Comparably high proportions (97 to 100 percent) of seven Chinese aboriginal populations possessed at least one ADH1C*1 allele, although the rates of homozygosity for ADH1C*1 were more variable (59 to 99 percent) in these populations (Chen et al. 1997; Shen et al. 1997; Thomasson et al. 1994). Finally, the prevalence of ADH1C*1 in one Korean Chinese sample was similar to the rates reported in Chinese samples, with 99 percent of subjects possessing at least one ADH1C*1 allele, including 86 percent who were homozygous for the allele (Shen et al. 1997).
Table 1. Genotypes for Genes Encoding Aldehyde Dehydrogenase (ALDH2) and Alcohol Dehydrogenase (ADH1B and ADH1C)
ALDH2 Genotypes prevalence (%)
ADH1B Genotypes prevalence (%)
ADH1C Genotypes prevalence (%)
Study Authors
Sample
*1/*1
*1/*2
*2/*2
*1/*1
*1/*2
*2/*2
*1/*1
*1/*2
*2/*2
Han Chinese and Taiwanese
Chao et al. 1987
60 male and 11 female liver specimens
10
31
59
Goedde et al. 1992
132 subjects*
70
29
1
8
48
44
Lee et al. 1989
53 lung specimens
9
30
60
Luo et al. 2001
50 subjects
78
20
2
Luo et al. 2005
444 males and 204 females
68
28
4
Novoradovsky et al. 1995
173 blood donors
45
47
8
Shen et al. 1997c
100 male
78
20
2
16
44
40
83
14
3
Total
66
30
4
11
40
49
83
14
3
Chinese American
Hendershot et al. 2005
110 male and 113 female college students
51
43
7
Luczak et al. 2004
92 males and 98 females college students
48
44
8
8
33
58
Total
49
43
7
8
33
58
Chinese and Taiwanese Aborigine
Chen et al. 1997
Ami
46 subjects*
93
7
0
22
38
40
98
2
0
Atayal
67 subjects*
97
3
0
0
21
79
96
4
0
Bunun
118 subjects*
98
2
0
1
30
69
88
12
0
Paiwan
71 subjects*
95
5
0
0
31
69
99
1
0
Shen et al. 1997
Elunchana
68 males
93
6
1
37
54
9
59
38
3
Mongolian
66 males
88
12
0
26
44
30
73
26
2
Thomasson et al. 1994
Atayala
80 males and 80 females*
94
5
1
3
24
74
97
3
0
Total
95
5
0
10
32
58
88
11
1
Filipino
Goedde et al. 1992
86 subjects*
99
1
0
19
40
40
Indian
Goedde et al. 1992a,b
179 subjects*
97
3
1
85
10
5
Japanese
Amamoto et al. 2002a
749 males and 1,286 females
48
45
7
Goedde et al. 1992
53 subjects*
55
43
2
16
50
34
Higuchi et al. 1996
230 male and 221 female hospital employees and relatives
59
35
6
7
35
58
Saito et al. 2003
335 males
53
41
6
8
35
57
Shibuya et al. 1989
15 males*
33
53
13
0
29
71
Sun et al. 1999
643 male hospital and civil service employees
58
36
6
4
35
61
Suzuki et al. 2004
1,126 males
5
34
61
Takeshita & Morimoto 1999
389 males and 34 females medical students
54
40
5
Takeshita et al. 1994
424 male and 100 females metal plant workers
57
37
7
Takeshita et al. 1996
424 male and 100 females metal plant workers
6
33
60
Tanaka et al. 1997a
189 males
51
48
1
5
38
57
Yamada et al. 2002
855 male factory workers
58
36
6
4
36
60
Yin et al. 1984b
97 liver samples
13
29
58
Yokoyama et al. 2005
139 male and 112 female workers
59
33
8
Total
54
40
6
6
35
60
Japanese American
Yin et al. 1984b
97 liver samples
19
34
47
Korean
Goedde et al. 1992
218 subjects*
72
27
2
4
31
65
Lee et al. 1997
481 subjects
71
26
3
Total
71
26
3
4
31
65
Korean American
Hendershot et al. 2005
97 male and 108 female college students
67
32
2
Luczak et al. 2004
107 male and 107 female college students
66
31
3
10
36
53
Total
66
32
2
10
36
53
Korean Chinese
Shen et al. 1997
105 males
63
34
3
11
38
50
86
13
1
Malay
Goedde et al. 1992
73 subjects*
93
7
0
17
48
35
Thai
Goedde et al. 1992
111 subjects
90
10
0
46
41
13
Siberian Yakut
Novoradovsky et al. 1995
209 subjects
100
0
0
a not in Hardy-Weinberg equilibrium for ALDH2; b not in Hardy-Weinberg equilibrium for ADH1B; c not in Hardy-Weinberg equilibrium for ADH1C; df = 1, p < .05 for all. * Sample size varies by gene analyzed.
SUMMARY
This literature review highlights the fact that the prevalence of ALDH2, ADH1B, and ADH1C alleles vary greatly across Asian ethnic groups. For example, whereas approximately half of Chinese-American and Japanese samples and approximately one-third of Korean and Han Chinese and Taiwanese studied carry at least one ALDH2*2 allele, the prevalence of this allele is much lower (10 percent) in Thais, and almost no Filipinos, Indians, or Chinese and Taiwanese aborigines carry the allele, with the exception of Mongolians (12 percent). Similarly, the ADH1B*2 allele is found in 80 percent or more of Han Chinese and Taiwanese, Filipino, Japanese, Korean, and some Chinese and Taiwanese aborigine people but only in about 15 percent of Indians. Finally, the ADH1C*1 allele was found in almost all Chinese and Korean people studied, but it has not been analyzed yet in other Asian ethnic groups. Such summaries of general-sample prevalence rates are important for understanding risk and protective factors for alcohol use disorders because they facilitate comparisons of the contribution of these alcohol-metabolizing enzymes and their variants to alcohol-related behaviors within and across ethnic groups.
ACKNOWLEDGEMENTS
This research was funded by National Institutes of Health grants K02–AA–00269, K08–AA–14265, R01–AA– 11257, and T32–AA–013525 and a grant from the Alcoholic Beverage Medical Research Foundation.
FINANCIAL DISCLOSURE
The authors declare that they have no competing financial interest.
REFERENCES
Amamoto, K.; Okamura, T.; Tamaki, S.; et al. Epidemiologic study of the association of low-Km mitochondrial acetaldehyde dehydrogenase genotypes with blood pressure level and the prevalence of hypertension in a general population. Hypertension Research 25:857–864, 2002. PMID: 12484509
Chao, T.-J.; Chang, C.-P.; Chang, M.-C.; et al. Liver alcohol and aldehyde dehydrogenase isoenzymes in Chinese. Proceedings of the National Science Council, Republic of China. Part B, Basic Science 11:260–265, 1987. PMID: 3423141
Chen, W.J.; Loh, E.W.; Hsu, Y.-P.P.; and Cheng, A.T.A. Alcohol dehydrogenase and aldehyde dehydrogenase and alcoholism among Taiwanese aborigines. Biological Psychiatry 41:703–709, 1997. PMID: 9066994
Eriksson, C.J.P. The role of acetaldehyde in actions of alcohol (Update 2000). Alcoholism: Clinical and Experimental Research 25:15S–32S, 2001. PMID: 11391045
Grant, B.F.; Stinson, F. S.; Dawson, D.A.; et al. Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. Archives of General Psychiatry 61:807–816, 2004. PMID: 15289279
Goedde, H.W.; Agarwal, D.P.; Fritze, G.; et al. Distribution of ADH2 and ALDH2 genotypes in different populations. Human Genetics 88:344–346, 1992. PMID: 1733836
Helzer, J.E.; Canino, G.J.; Yeh, E.-K.; et al. Alcoholism: North America and Asia. Archives of General Psychiatry 47:313–319, 1990. PMID: 2322082
Hendershot, C.S.; MacPherson, L.; Myers, M.G.; et al. Psychosocial, cultural and genetic influences on alcohol use in Asian American youth. Journal of Studies on Alcohol 66:185–195, 2005. PMID: 15957669
Higuchi, S.; Matsushita, S.; Muramatsu, T.; et al. Alcohol and aldehyde dehydrogenase genotypes and drinking behavior in Japanese. Alcoholism: Clinical and Experimental Research 20:493–497, 1996. PMID: 8727242
Lee, K.-H.; Kwak, B.-Y.; Kim, J.-H.; et al. Genetic polymorphism of cytochrome P-450E1 and mitochrondrial aldehyde dehydrogenase in a Korean population. Alcoholism: Clinical and Experimental Research 21:953–956, 1997. PMID: 9309300
Lee, S.-C.; Lin, J.-S.; Chou, F.-J; and Yin, S.-J. Lung alcohol and aldehyde dehydrogenase isoenzymes in Chinese. Journal of the Formosan Medical Association 88:437–442, 1989. PMID: 2677229
Luczak, S.E.; Wall, T.L.; Cook, T.A.R.; et al. ALDH2 status and conduct disorder mediate the relationship between ethnicity and alcohol dependence in Chinese-, Korean-, and White-American college students. Journal of Abnormal Psychology 113:271–278, 2004. PMID: 15122947
Luczak, S.E.; Glatt, S.J.; and Wall, T.L. Meta-analyses of ALDH2 and ADH1B with alcohol dependence in Asians. Psychological Bulletin 132:607– 612, 2006. PMID: 16822169
Luo, H.-R.; Tu, G.-C; and Zhang, Y.-P. Detection of usual and atypical aldehyde dehydrogenase alleles by mismatch amplification mutation assay. Clinical Chemistry and Laboratory Medicine: CCLM/FESCC 39:1195–1197, 2001. PMID: 11798074
Luo, H.-R.; Israel, Y.; Tu, G.-C.; et al. Genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) in a Chinese population: Gender, age, culture, and genotypes of ALDH2. Biochemical Genetics 43:223–227, 2005. PMID: 16144299
Novoradovsky, A.; Tsai, S.-J. L.; Goldfarb, L.; et al. Mitochondrial aldehyde dehydrogenase polymorphism in Asian and American Indian Populations: Detection of new ALDH2 alleles. Alcoholism: Clinical and Experimental Research 5:1105–1110, 1995. PMID: 8561277
Osier, M.; Pakstis, A.J.; Kidd, J.R.; et al. Linkage disequilibrium at the ADH2 and ADH3 loci and risk for alcoholism. American Journal of Human Genetics 64:1147–1157, 1999. PMID: 10090900
Saito, K.; Yokoyama, T.; Yoshiike, N.; et al. Do the ethanol metabolizing enzymes modify the relationship between alcohol consumption and blood pressure? Journal of Hypertension 21:1097–1105, 2003. PMID: 12777946
Shen, Y.-C.; Fan, J.-H.; Edenberg, H.J.; et al. Polymorphism of ADH and ALDH genes among four ethnic groups in China and effects upon the risk for alcoholism. Alcoholism: Clinical and Experimental Research 21:1272–1277, 1997. PMID: 9347089
Shibuya, A.; Yasunami, M.; and Yoshida, A. Genotypes of alcohol dehydrogenase and aldehyde dehydrogenase loci in Japanese alcohol flushers and nonflushers. Human Genetics 82:14–16, 1989. PMID: 2714775
Sun, F.; Tsuritani, I.; Honda, R.; et al. Association of genetic polymorphisms of alcohol metabolizing enzymes with excessive alcohol consumption in Japanese men. Human Genetics 105:295–300, 1999. PMID: 10543395
Suzuki, Y.; Fujisawa, M.; Ando, F.; et al. Alcohol dehydrogenase 2 variant is associated with cerebral infarction and lacunae. Neurology 63:1711–1713, 2004. PMID: 15534263
Takeshita, T., and Morimoto, K. Self-reported alcohol-associated symptoms and drinking behavior in three ALDH2 genotypes among Japanese university students. Alcoholism: Clinical and Experimental Research 23:1065–1069, 1999. PMID: 10397292
Takeshita, T.; Morimoto, K.; Mao, X.Q.; et al. Characterization of the three genotypes of low Km aldehyde dehydrogenase in a Japanese population. Human Genetics 94:217–223, 1994. PMID: 8076934
Takeshita, T.; Mao, X.-Q.; and Morimoto, K. The contribution of polymorphism in the alcohol dehydrogenase b subunit to alcohol sensitivity in a Japanese population. Human Genetics 97:409–413, 1996. PMID: 8834233
Tanaka, R.; Shiratori, Y.; Yokosuka, O.; et al. Polymorphism of alcohol-metabolizing genes affects drinking behavior and alcoholic liver disease in Japanese men. Alcoholism: Clinical and Experimental Research 21:596–601, 1997. PMID: 9194910
Thomasson, H.R.; Crabb, D.W.; Edenberg, H.J.; et al. Low frequency of the ADH2*2 allele among Atayal natives of Taiwan with alcohol use disorders. Alcoholism: Clinical and Experimental Research 18:640–643, 1994. PMID: 7943668
Wall, T.L.; Shea, S.H.; Luczak, S.E.; et al. Genetic associations of alcohol dehydrogenase with alcohol use disorders and endophenotypes in White college students. Journal of Abnormal Psychology 114:456–465, 2005. PMID: 16117582
Yamada, Y.; Sun, F.; Tsuritani, I.; and Honda, R. Genetic differences in ethanol metabolizing enzymes and blood pressure in Japanese alcohol consumers. Journal of Human Hypertension 16:479–486, 2002. PMID: 12080432
Yin, S.-J.; Bosron, R.F.; Li, T.-K.; et al. Polymorphism of human liver alcohol dehydrogenase: Identification of ADH2 2-1 and ADH2 2-2 phenotypes in the Japanese by isoelectric focusing. Biochemical Genetics 22:169–180, 1984.
Yokoyama, M.; Yokoyama, A.; Yokoyama, T.; et al. Hangover susceptibility in relation to aldehyde dehydrogenase-2 genotype, alcohol flushing, and mean corpuscular volume in Japanese workers. Alcoholism: Clinical and Experimental Research 29:1165–1171, 2005. PMID: 16046871
| ||||||||||||||