| Further clarification of the contribution of the ADH1C gene to vulnerability of alcoholism and selected liver diseases. | |
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MedLine Citation:
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PMID: 22476623 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The alcohol dehydrogenase 1C (ADH1C) subunit is an important member of the alcohol dehydrogenase family, a set of genes that plays a major role in the catabolism of ethanol. Numerous association studies have provided compelling evidence that ADH1C gene variation (formerly ADH3) is associated with altered genetic susceptibility to alcoholism and alcohol-related liver disease, cirrhosis, or pancreatitis. However, the results have been inconsistent, partially, because each study involved a limited number of subjects, and some were underpowered. Using cumulative data over the past two decades, this meta-analysis (6,796 cases and 6,938 controls) considered samples of Asian, European, African, and Native American origins to examine whether the aggregate genotype provide statistically significant evidence of association. The results showed strong evidence of association between ADH1C Ile350Val (rs698, formerly ADH1C *1/*2) and alcohol dependence (AD) and abuse in the combined studies. The overall allelic (Val vs. Ile or *2 vs. *1) P value was 1 × 10(-8) and odds ratio (OR) was 1.51 (1.31, 1.73). The Asian populations produced stronger evidence of association with an allelic P value of 4 × 10(-33) [OR 2.14 (1.89, 2.43)] with no evidence of heterogeneity, and the dominant and recessive models revealed even stronger effect sizes. The strong evidence remained when stricter criteria and sub-group analyses were applied, while Asians always showed stronger associations than other populations. Our findings support that ADH1C Ile may lower the risk of AD and alcohol abuse as well as alcohol-related cirrhosis in pooled populations, with the strongest and most consistent effects in Asians. |
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Authors:
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Dawei Li; Hongyu Zhao; Joel Gelernter |
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Publication Detail:
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Type: Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural Date: 2012-04-05 |
Journal Detail:
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Title: Human genetics Volume: 131 ISSN: 1432-1203 ISO Abbreviation: Hum. Genet. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-07-16 Completed Date: 2012-09-17 Revised Date: 2013-05-06 |
Medline Journal Info:
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Nlm Unique ID: 7613873 Medline TA: Hum Genet Country: Germany |
Other Details:
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Languages: eng Pagination: 1361-74 Citation Subset: IM |
Affiliation:
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Department of Psychiatry, School of Medicine, Yale University, 300 George Street, Suite 503, New Haven, CT 06511, USA. dawei.li@yale.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alcohol Dehydrogenase
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genetics* Alcoholism / genetics* Genetic Predisposition to Disease* Humans Liver Diseases / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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AA017535/AA/NIAAA NIH HHS; AA11330/AA/NIAAA NIH HHS; AA12870/AA/NIAAA NIH HHS; DA12690/DA/NIDA NIH HHS; DA12849/DA/NIDA NIH HHS; P50 AA012870/AA/NIAAA NIH HHS; R01 AA011330/AA/NIAAA NIH HHS; R01 AA017535/AA/NIAAA NIH HHS; R01 DA012690/DA/NIDA NIH HHS; R01 DA012849/DA/NIDA NIH HHS; UL1 TR000142/TR/NCATS NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 1.1.1.1/ADH1C protein, human; EC 1.1.1.1/Alcohol Dehydrogenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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