Yonsei Med J.  2016 Jul;57(4):879-884. 10.3349/ymj.2016.57.4.879.

Aldehyde Dehydrogenase 2 (ALDH2) Polymorphism and the Risk of Alcoholic Liver Cirrhosis among East Asians: A Meta-Analysis

Affiliations
  • 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China. dengtao1120@hotmail.com

Abstract

PURPOSE
The aldehyde dehydrogenase 2 (ALDH2) gene has been implicated in the development of alcoholic liver cirrhosis (ALC) in East Asians. However, the results are inconsistent. In this study, a meta-analysis was performed to assess the associations between the ALDH2 polymorphism and the risk of ALC.
MATERIALS AND METHODS
Relevant studies were retrieved by searching PubMed, Web of Science, CNKI, Wanfang and Veipu databases up to January 10, 2015. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using either the fixed- or random effects model.
RESULTS
A total of twelve case-control studies included 1003 cases and 2011 controls were included. Overall, the ALDH2 polymorphism was associated with a decreased risk of ALC (*1/*2 vs. *1/*1: OR=0.78, 95% CI: 0.61-0.99). However, in stratification analysis by country, we failed to detect any association among Chinese, Korean or Japanese populations.
CONCLUSION
The pooled evidence suggests that ALDH2 polymorphism may be an important protective factor for ALC in East Asians.

Keyword

ALDH2; polymorphism; alcoholic liver cirrhosis; meta-analysis

MeSH Terms

Aldehyde Dehydrogenase, Mitochondrial/*genetics
Asian Continental Ancestry Group/*genetics
Case-Control Studies
Genetic Predisposition to Disease
Humans
Liver Cirrhosis, Alcoholic/*ethnology/*genetics
Odds Ratio
Polymorphism, Genetic/*genetics
Protective Factors
Aldehyde Dehydrogenase, Mitochondrial

Figure

  • Fig. 1 The flow chart of study selection based on the inclusion and exclusion criteria. ALDH2, aldehyde dehydrogenase 2.

  • Fig. 2 Forest plots for the association of ALDH2 and alcoholic cirrhosis risk (*1/*2 vs. *1/*1). ALDH2, aldehyde dehydrogenase 2; CI, confidence interval.

  • Fig. 3 Subgroup analysis of odds ratios by country for association between ALDH2 polymorphism and risk of alcoholic liver cirrhosis (*1/*2 vs. *1/*1). ALDH2, aldehyde dehydrogenase 2; CI, confidence interval.

  • Fig. 4 Begg's funnel plot of publication bias test for ALDH2 and alcoholic cirrhosis risk (*1/*2 vs. *1/*1). ALDH2, aldehyde dehydrogenase 2; OR, odds ratio.


Cited by  2 articles

Association between Alcohol Consumption and Serum Cortisol Levels: a Mendelian Randomization Study
Jung-Ho Yang, Sun-Seog Kweon, Young-Hoon Lee, Seong-Woo Choi, So-Yeon Ryu, Hae-Sung Nam, Kyeong-Soo Park, Hye-Yeon Kim, Min-Ho Shin
J Korean Med Sci. 2021;36(30):e195.    doi: 10.3346/jkms.2021.36.e195.

Alcohol Consumption, Aldehyde Dehydrogenase 2 Gene Polymorphisms, and Cardiovascular Health in Korea
Min-Jeong Shin, Yoonsu Cho, George Davey Smith
Yonsei Med J. 2017;58(4):689-696.    doi: 10.3349/ymj.2017.58.4.689.


Reference

1. Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet. 2009; 373:2223–2233.
Article
2. O'Shea RS, Dasarathy S, McCullough AJ. Practice Guideline Committee of the American Association for the Study of Liver Diseases. Practice Parameters Committee of the American College of Gastroenterology. Alcoholic liver disease. Hepatology. 2010; 51:307–328.
3. Monzoni A, Masutti F, Saccoccio G, Bellentani S, Tiribelli C, Giacca M. Genetic determinants of ethanol-induced liver damage. Mol Med. 2001; 7:255–262.
Article
4. Stickel F, Hampe J. Genetic determinants of alcoholic liver disease. Gut. 2012; 61:150–159.
Article
5. Yoshida A, Rzhetsky A, Hsu LC, Chang C. Human aldehyde dehydrogenase gene family. Eur J Biochem. 1998; 251:549–557.
Article
6. Mizoi Y, Yamamoto K, Ueno Y, Fukunaga T, Harada S. Involvement of genetic polymorphism of alcohol and aldehyde dehydrogenases in individual variation of alcohol metabolism. Alcohol Alcohol. 1994; 29:707–710.
7. Goedde HW, Agarwal DP, Fritze G, Meier-Tackmann D, Singh S, Beckmann G, et al. Distribution of ADH2 and ALDH2 genotypes in different populations. Hum Genet. 1992; 88:344–346.
Article
8. Chao YC, Liou SR, Chung YY, Tang HS, Hsu CT, Li TK, et al. Polymorphism of alcohol and aldehyde dehydrogenase genes and alcoholic cirrhosis in Chinese patients. Hepatology. 1994; 19:360–366.
Article
9. Chao YC, Young TH, Tang HS, Hsu CT. Alcoholism and alcoholic organ damage and genetic polymorphisms of alcohol metabolizing enzymes in Chinese patients. Hepatology. 1997; 25:112–117.
Article
10. Chao YC, Wang LS, Hsieh TY, Chu CW, Chang FY, Chu HC. Chinese alcoholic patients with esophageal cancer are genetically different from alcoholics with acute pancreatitis and liver cirrhosis. Am J Gastroenterol. 2000; 95:2958–2964.
Article
11. Chao YC, Wang SJ, Chu HC, Chang WK, Hsieh TY. Investigation of alcohol metabolizing enzyme genes in Chinese alcoholics with avascular necrosis of hip joint, pancreatitis and cirrhosis of the liver. Alcohol Alcohol. 2003; 38:431–436.
Article
12. Kee JY, Kim MO, You IY, Chai JY, Hong ES, An SC, et al. Effects of genetic polymorphisms of ethanol-metabolizing enzymes on alcohol drinking behaviors. Korean J Hepatol. 2003; 9:89–97.
13. Kim MS, Lee DH, Kang HS, Park HS, Jung S, Lee JW, et al. Genetic polymorphisms of alcohol-metabolizing enzymes and cytokines in patients with alcohol induced pancreatitis and alcoholic liver cirrhosis. Korean J Gastroenterol. 2004; 43:355–363.
14. Lee HC, Lee HS, Jung SH, Yi SY, Jung HK, Yoon JH, et al. Association between polymorphisms of ethanol-metabolizing enzymes and susceptibility to alcoholic cirrhosis in a Korean male population. J Korean Med Sci. 2001; 16:745–750.
Article
15. Nagata N, Watanabe N, Tsuda M, Tsukamoto H, Matsuzaki S. Relationship between serum levels of anti-low-density lipoproteinacetaldehyde-adduct antibody and aldehyde dehydrogenase 2 heterozygotes in patients with alcoholic liver injury. Alcohol Clin Exp Res. 1999; 23:4 Suppl. 24S–28S.
Article
16. Nagata N, Hiyoshi M, Shiozawa H, Shiraishi K, Watanabe N, Tsuda M, et al. Assessment of a difference in ALDH2 heterozygotes and alcoholic liver injury. Alcohol Clin Exp Res. 2002; 26:8 Suppl. 11S–14S.
Article
17. Yamauchi M, Maezawa Y, Mizuhara Y, Ohata M, Hirakawa J, Nakajima H, et al. Polymorphisms in alcohol metabolizing enzyme genes and alcoholic cirrhosis in Japanese patients: a multivariate analysis. Hepatology. 1995; 22(4 Pt 1):1136–1142.
Article
18. Yamauchi M, Maezawa Y, Toda G, Suzuki H, Sakurai S. Association of a restriction fragment length polymorphism in the alcohol dehydrogenase 2 gene with Japanese alcoholic liver cirrhosis. J Hepatol. 1995; 23:519–523.
Article
19. Yokoyama A, Mizukami T, Matsui T, Yokoyama T, Kimura M, Matsushita S, et al. Genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and liver cirrhosis, chronic calcific pancreatitis, diabetes mellitus, and hypertension among Japanese alcoholic men. Alcohol Clin Exp Res. 2013; 37:1391–1401.
Article
20. Day CP, Bashir R, James OF, Bassendine MF, Crabb DW, Thomasson HR, et al. Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage. Hepatology. 1991; 14:798–801.
Article
21. Frenzer A, Butler WJ, Norton ID, Wilson JS, Apte MV, Pirola RC, et al. Polymorphism in alcohol-metabolizing enzymes, glutathione S-transferases and apolipoprotein E and susceptibility to alcoholinduced cirrhosis and chronic pancreatitis. J Gastroenterol Hepatol. 2002; 17:177–182.
Article
22. García-Bañuelos J, Panduro A, Gordillo-Bastidas D, Gordillo-Bastidas E, Muñoz-Valle JF, Gurrola-Díaz CM, et al. Genetic polymorphisms of genes coding to alcohol-metabolizing enzymes in western Mexicans: association of CYP2E1*c2/CYP2E1*5B allele with cirrhosis and liver function. Alcohol Clin Exp Res. 2012; 36:425–431.
Article
23. Kato S, Tajiri T, Matsukura N, Matsuda N, Taniai N, Mamada H, et al. Genetic polymorphisms of aldehyde dehydrogenase 2, cytochrome p450 2E1 for liver cancer risk in HCV antibody-positive japanese patients and the variations of CYP2E1 mRNA expression levels in the liver due to its polymorphism. Scand J Gastroenterol. 2003; 38:886–893.
Article
24. Ohhira M, Fujimoto Y, Matsumoto A, Ohtake T, Ono M, Kohgo Y. Hepatocellular carcinoma associated with alcoholic liver disease: a clinicopathological study and genetic polymorphism of aldehyde dehydrogenase 2. Alcohol Clin Exp Res. 1996; 20:9 Suppl. 378A–382A.
25. Tanaka F, Shiratori Y, Yokosuka O, Imazeki F, Tsukada Y, Omata M. High incidence of ADH2*1/ALDH2*1 genes among Japanese alcohol dependents and patients with alcoholic liver disease. Hepatology. 1996; 23:234–239.
Article
26. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997; 127:820–826.
Article
27. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959; 22:719–748.
28. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986; 7:177–188.
Article
29. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994; 50:1088–1101.
Article
30. Egger M, Davey Smith G, Schneider M, Minder C. Bias in metaanalysis detected by a simple, graphical test. BMJ. 1997; 315:629–634.
Article
31. Eriksson CJ. The role of acetaldehyde in the actions of alcohol (update 2000). Alcohol Clin Exp Res. 2001; 25:5 Suppl ISBRA. 15S–32S.
Article
32. Yoshida A, Hsu LC, Yasunami M. Genetics of human alcohol-metabolizing enzymes. Prog Nucleic Acid Res Mol Biol. 1991; 40:255–287.
Article
33. Goedde HW, Agarwal DP. Acetaldehyde metabolism: genetic variation and physiological implications. In : Goedde HW, Agarwal DP, editors. Alcoholism: Biomedical and Genetic Aspects. Elmsford: Pergamon Press;1989. p. 21–56.
34. Zintzaras E, Stefanidis I, Santos M, Vidal F. Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease? Hepatology. 2006; 43:352–361.
Article
35. Li D, Zhao H, Gelernter J. Strong protective effect of the aldehyde dehydrogenase gene (ALDH2) 504lys (*2) allele against alcoholism and alcohol-induced medical diseases in Asians. Hum Genet. 2012; 131:725–737.
Article
36. Enomoto N, Takase S, Yasuhara M, Takada A. Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes. Alcohol Clin Exp Res. 1991; 15:141–144.
Article
37. Thomasson HR, Edenberg HJ, Crabb DW, Mai XL, Jerome RE, Li TK, et al. Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men. Am J Hum Genet. 1991; 48:677–681.
38. Murayama M, Matsushita S, Muramatsu T, Higuchi S. Clinical characteristics and disease course of alcoholics with inactive aldehyde dehydrogenase-2. Alcohol Clin Exp Res. 1998; 22:524–527.
Article
39. Nuutinen H, Lindros KO, Salaspuro M. Determinants of blood acetaldehyde level during ethanol oxidation in chronic alcoholics. Alcohol Clin Exp Res. 1983; 7:163–168.
Article
40. Yokoyama A, Tsutsumi E, Imazeki H, Suwa Y, Nakamura C, Yokoyama T. Polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and the blood and salivary ethanol and acetaldehyde concentrations of Japanese alcoholic men. Alcohol Clin Exp Res. 2010; 34:1246–1256.
Article
Full Text Links
  • YMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr