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  •   University of Thessaly Institutional Repository
  • Επιστημονικές Δημοσιεύσεις Μελών ΠΘ (ΕΔΠΘ)
  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ.
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  •   University of Thessaly Institutional Repository
  • Επιστημονικές Δημοσιεύσεις Μελών ΠΘ (ΕΔΠΘ)
  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ.
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Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?

Thumbnail
Author
Zintzaras, E.; Stefanidis, I.; Santos, M.; Vidal, F.
Date
2006
DOI
10.1002/hep.21023
Keyword
alcohol dehydrogenase
aldehyde dehydrogenase
aldehyde dehydrogenase isoenzyme 2
cytochrome P450 2E1
adh2 gene
adh3 gene
adlh2 gene
alcohol liver disease
alcoholism
allele
article
clinical trial
disease association
DNA polymorphism
ethnic difference
gene
genetic heterogeneity
human
liver injury
meta analysis
priority journal
risk assessment
sensitivity analysis
statistical analysis
systematic review
Asian Continental Ancestry Group
Case-Control Studies
Cytochrome P-450 CYP2E1
Ethanol
European Continental Ancestry Group
Gene Frequency
Humans
Liver Diseases, Alcoholic
Polymorphism, Genetic
Risk
Metadata display
Abstract
Case-control studies that have investigated the association between alcoholism and alcohol-induced liver damage and the ADH2, ADH3, CYP2E1, and ADLH2 polymorphisms have reported controversial or inconclusive results. Thus, we conducted a meta-analysis of 50 association studies of the above polymorphisms. We explored potential sources of heterogeneity and bias, performed subgroup analyses by racial background and sex, performed sensitivity analyses for studies not in Hardy-Weinberg equilibrium, and performed a subgroup analysis for cases that met strict criteria for alcoholism. The present meta-analysis underscores significant associations of ADH2*1, ADH3*2, and ALDH2*1 alleles and the risk of alcoholism (OR = 1.89 [95% CI 1.56-2.28], 1.32 [95% CI 1.12-1.57], and 4.35 [95% CI 3.04-6.23], respectively). The subsequent subgroup analyses showed association for ADH2*1 and ADH3*2 only in East Asians (OR = 2.23 [95% CI 1.81-2.74] and 1.91 [95% CI 1.45-2.53], respectively) and East Asian males (OR = 2.21 [95% CI 1.57-3.10], 1.69 [95% CI 1.10-2.59], respectively). In East Asian males, the OR for ALDH2*1 was 3.66 (95% CI 1.68-7.96). In Caucasians, sensitivity analysis revealed an association for ADH2*1 in alcoholism (OR = 1.62 [95% CI 1.22-1.89]). When strict criteria were imposed, the pattern of results remained unaltered. For liver disease, there were no significant associations for ADH2*1, ADH3*2, or ALDH2*1 in all subpopulations. The CYP2E1 polymorphism showed no association whatsoever. There is evidence that alleles are mainly dominant. In conclusion, there was heterogeneity between studies in alcoholism for ADH2, ADH3, and ALDH2, and lack of bias in all polymorphisms. The above findings reinforce the need for more rigorous studies, and for regular synthesis of studies' results. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/ jpages/0270-9139/suppmat/index.html). Copyright © 2006 by the American Association for the Study of Liver Diseases.
URI
http://hdl.handle.net/11615/34981
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  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ. [19672]

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