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Meta‐analysis: glutathione‐S‐transferase allelic variants are associated with alcoholic liver disease
Aliment Pharmacol Ther 2011; 34: 1159–1172 Summary Background Only a minority of alcoholics develop alcoholic liver disease (ALD) and allelic variants within genes encoding glutathione‐S‐transferases (GST) have been associated with ALD vulnerability with controversial results. Aim To assess the ef...
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Published in: | Alimentary pharmacology & therapeutics 2011-11, Vol.34 (10), p.1159-1172 |
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creator | Marcos, M. Pastor, I. Chamorro, A.‐J. Ciria‐Abad, S. González‐Sarmiento, R. Laso, F.‐J. |
description | Aliment Pharmacol Ther 2011; 34: 1159–1172
Summary
Background Only a minority of alcoholics develop alcoholic liver disease (ALD) and allelic variants within genes encoding glutathione‐S‐transferases (GST) have been associated with ALD vulnerability with controversial results.
Aim To assess the effects of GST polymorphisms on ALD by means of a genetic association study and meta‐analysis.
Methods We retrieved published studies on the relationship between allelic variants within GST genes and ALD by means of electronic database search. A meta‐analysis was conducted in a fixed or random effects model. Calculations of odds ratios (OR) and their confidence intervals (CI), tests for heterogeneity of the results and sensitivity analysis, have been performed. A genetic association study comparing GSTM1, GSTT1 and GSTP1 genotype distribution among 279 alcoholics with or without ALD and 144 controls was also performed.
Results Fifteen previous studies were identified analysing the association of ALD with polymorphisms within GST genes. After meta‐analysis, we found a significant association between the possession of the GSTM1 null allele and the presence of ALD (OR = 1.43; 95% CI: 1.14, 1.78; P = 0.002) among alcoholic patients. A significant association was also found for the possession of the GSTP1 Val/Val genotype and the presence of ALD (OR = 2.04; 95% CI: 1.09, 3.80; P = 0.03).
Conclusions Our results suggest that, among alcoholics, carriers of GSTM1 null genetic variant or Val/Val genotype of Ile/Val GSTP1 polymorphism have an increased risk to suffer from alcoholic liver disease. The role of glutathione‐S‐transferase as a potential therapeutic target in alcoholic liver disease is reinforced. |
doi_str_mv | 10.1111/j.1365-2036.2011.04862.x |
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Summary
Background Only a minority of alcoholics develop alcoholic liver disease (ALD) and allelic variants within genes encoding glutathione‐S‐transferases (GST) have been associated with ALD vulnerability with controversial results.
Aim To assess the effects of GST polymorphisms on ALD by means of a genetic association study and meta‐analysis.
Methods We retrieved published studies on the relationship between allelic variants within GST genes and ALD by means of electronic database search. A meta‐analysis was conducted in a fixed or random effects model. Calculations of odds ratios (OR) and their confidence intervals (CI), tests for heterogeneity of the results and sensitivity analysis, have been performed. A genetic association study comparing GSTM1, GSTT1 and GSTP1 genotype distribution among 279 alcoholics with or without ALD and 144 controls was also performed.
Results Fifteen previous studies were identified analysing the association of ALD with polymorphisms within GST genes. After meta‐analysis, we found a significant association between the possession of the GSTM1 null allele and the presence of ALD (OR = 1.43; 95% CI: 1.14, 1.78; P = 0.002) among alcoholic patients. A significant association was also found for the possession of the GSTP1 Val/Val genotype and the presence of ALD (OR = 2.04; 95% CI: 1.09, 3.80; P = 0.03).
Conclusions Our results suggest that, among alcoholics, carriers of GSTM1 null genetic variant or Val/Val genotype of Ile/Val GSTP1 polymorphism have an increased risk to suffer from alcoholic liver disease. The role of glutathione‐S‐transferase as a potential therapeutic target in alcoholic liver disease is reinforced.</description><identifier>ISSN: 0269-2813</identifier><identifier>EISSN: 1365-2036</identifier><identifier>DOI: 10.1111/j.1365-2036.2011.04862.x</identifier><identifier>PMID: 21967547</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Alcoholics ; Alcoholism - genetics ; Alleles ; Biological and medical sciences ; Digestive system ; Gastroenterology. Liver. Pancreas. Abdomen ; Genetic Predisposition to Disease ; Glutathione Transferase - genetics ; Humans ; Liver Diseases, Alcoholic - genetics ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Other diseases. Semiology ; Pharmacology. Drug treatments ; Polymorphism, Genetic ; Risk Factors</subject><ispartof>Alimentary pharmacology & therapeutics, 2011-11, Vol.34 (10), p.1159-1172</ispartof><rights>2011 Blackwell Publishing Ltd</rights><rights>2015 INIST-CNRS</rights><rights>2011 Blackwell Publishing Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3492-aebda3f404343e31d8142c9dc9e54f4b57e4d11311c163694211e2c04a8ab1703</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24618694$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21967547$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marcos, M.</creatorcontrib><creatorcontrib>Pastor, I.</creatorcontrib><creatorcontrib>Chamorro, A.‐J.</creatorcontrib><creatorcontrib>Ciria‐Abad, S.</creatorcontrib><creatorcontrib>González‐Sarmiento, R.</creatorcontrib><creatorcontrib>Laso, F.‐J.</creatorcontrib><title>Meta‐analysis: glutathione‐S‐transferase allelic variants are associated with alcoholic liver disease</title><title>Alimentary pharmacology & therapeutics</title><addtitle>Aliment Pharmacol Ther</addtitle><description>Aliment Pharmacol Ther 2011; 34: 1159–1172
Summary
Background Only a minority of alcoholics develop alcoholic liver disease (ALD) and allelic variants within genes encoding glutathione‐S‐transferases (GST) have been associated with ALD vulnerability with controversial results.
Aim To assess the effects of GST polymorphisms on ALD by means of a genetic association study and meta‐analysis.
Methods We retrieved published studies on the relationship between allelic variants within GST genes and ALD by means of electronic database search. A meta‐analysis was conducted in a fixed or random effects model. Calculations of odds ratios (OR) and their confidence intervals (CI), tests for heterogeneity of the results and sensitivity analysis, have been performed. A genetic association study comparing GSTM1, GSTT1 and GSTP1 genotype distribution among 279 alcoholics with or without ALD and 144 controls was also performed.
Results Fifteen previous studies were identified analysing the association of ALD with polymorphisms within GST genes. After meta‐analysis, we found a significant association between the possession of the GSTM1 null allele and the presence of ALD (OR = 1.43; 95% CI: 1.14, 1.78; P = 0.002) among alcoholic patients. A significant association was also found for the possession of the GSTP1 Val/Val genotype and the presence of ALD (OR = 2.04; 95% CI: 1.09, 3.80; P = 0.03).
Conclusions Our results suggest that, among alcoholics, carriers of GSTM1 null genetic variant or Val/Val genotype of Ile/Val GSTP1 polymorphism have an increased risk to suffer from alcoholic liver disease. The role of glutathione‐S‐transferase as a potential therapeutic target in alcoholic liver disease is reinforced.</description><subject>Alcoholics</subject><subject>Alcoholism - genetics</subject><subject>Alleles</subject><subject>Biological and medical sciences</subject><subject>Digestive system</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Genetic Predisposition to Disease</subject><subject>Glutathione Transferase - genetics</subject><subject>Humans</subject><subject>Liver Diseases, Alcoholic - genetics</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Other diseases. Semiology</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism, Genetic</subject><subject>Risk Factors</subject><issn>0269-2813</issn><issn>1365-2036</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNpFkcFO3DAQQK0KVLaUX6hyQZySemyvE1figFa0IIGoVDhbs86k6603gTgL7K2fwDfyJXXKApZGtmbeWKN5jGXAC0jn67IAqae54FIXggMUXFVaFI8f2OStsMMmXGiTiwrkHvsU45JzrksuPrI9AUaXU1VO2J9LGvD57xO2GDbRx2_Z77AecFj4rqWU_5Vi6LGNDfUYKcMQKHiX3WPvsR1ihn1Kxtg5jwPV2YMfFgly3aIbseDvqc9qHyk1f2a7DYZIB9t7n918P72eneUXVz_OZycXuZPKiBxpXqNsFFdSSZJQV6CEM7UzNFWNmk9LUjWABHCgpTZKAJBwXGGFcyi53GdHL__e9t3dmuJgVz46CgFb6tbRVsaAlNJUifyyJdfzFdX2tvcr7Df2dT8JONwCGB2GJm3C-fjOKQ1VmiBxxy_cgw-0easDt6Mvu7SjFjtqsaMv-9-XfbQnP6_Hl_wH8FCMSA</recordid><startdate>201111</startdate><enddate>201111</enddate><creator>Marcos, M.</creator><creator>Pastor, I.</creator><creator>Chamorro, A.‐J.</creator><creator>Ciria‐Abad, S.</creator><creator>González‐Sarmiento, R.</creator><creator>Laso, F.‐J.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201111</creationdate><title>Meta‐analysis: glutathione‐S‐transferase allelic variants are associated with alcoholic liver disease</title><author>Marcos, M. ; Pastor, I. ; Chamorro, A.‐J. ; Ciria‐Abad, S. ; González‐Sarmiento, R. ; Laso, F.‐J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3492-aebda3f404343e31d8142c9dc9e54f4b57e4d11311c163694211e2c04a8ab1703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Alcoholics</topic><topic>Alcoholism - genetics</topic><topic>Alleles</topic><topic>Biological and medical sciences</topic><topic>Digestive system</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Genetic Predisposition to Disease</topic><topic>Glutathione Transferase - genetics</topic><topic>Humans</topic><topic>Liver Diseases, Alcoholic - genetics</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Other diseases. Semiology</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism, Genetic</topic><topic>Risk Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marcos, M.</creatorcontrib><creatorcontrib>Pastor, I.</creatorcontrib><creatorcontrib>Chamorro, A.‐J.</creatorcontrib><creatorcontrib>Ciria‐Abad, S.</creatorcontrib><creatorcontrib>González‐Sarmiento, R.</creatorcontrib><creatorcontrib>Laso, F.‐J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Alimentary pharmacology & therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marcos, M.</au><au>Pastor, I.</au><au>Chamorro, A.‐J.</au><au>Ciria‐Abad, S.</au><au>González‐Sarmiento, R.</au><au>Laso, F.‐J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Meta‐analysis: glutathione‐S‐transferase allelic variants are associated with alcoholic liver disease</atitle><jtitle>Alimentary pharmacology & therapeutics</jtitle><addtitle>Aliment Pharmacol Ther</addtitle><date>2011-11</date><risdate>2011</risdate><volume>34</volume><issue>10</issue><spage>1159</spage><epage>1172</epage><pages>1159-1172</pages><issn>0269-2813</issn><eissn>1365-2036</eissn><abstract>Aliment Pharmacol Ther 2011; 34: 1159–1172
Summary
Background Only a minority of alcoholics develop alcoholic liver disease (ALD) and allelic variants within genes encoding glutathione‐S‐transferases (GST) have been associated with ALD vulnerability with controversial results.
Aim To assess the effects of GST polymorphisms on ALD by means of a genetic association study and meta‐analysis.
Methods We retrieved published studies on the relationship between allelic variants within GST genes and ALD by means of electronic database search. A meta‐analysis was conducted in a fixed or random effects model. Calculations of odds ratios (OR) and their confidence intervals (CI), tests for heterogeneity of the results and sensitivity analysis, have been performed. A genetic association study comparing GSTM1, GSTT1 and GSTP1 genotype distribution among 279 alcoholics with or without ALD and 144 controls was also performed.
Results Fifteen previous studies were identified analysing the association of ALD with polymorphisms within GST genes. After meta‐analysis, we found a significant association between the possession of the GSTM1 null allele and the presence of ALD (OR = 1.43; 95% CI: 1.14, 1.78; P = 0.002) among alcoholic patients. A significant association was also found for the possession of the GSTP1 Val/Val genotype and the presence of ALD (OR = 2.04; 95% CI: 1.09, 3.80; P = 0.03).
Conclusions Our results suggest that, among alcoholics, carriers of GSTM1 null genetic variant or Val/Val genotype of Ile/Val GSTP1 polymorphism have an increased risk to suffer from alcoholic liver disease. The role of glutathione‐S‐transferase as a potential therapeutic target in alcoholic liver disease is reinforced.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21967547</pmid><doi>10.1111/j.1365-2036.2011.04862.x</doi><tpages>14</tpages></addata></record> |
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subjects | Alcoholics Alcoholism - genetics Alleles Biological and medical sciences Digestive system Gastroenterology. Liver. Pancreas. Abdomen Genetic Predisposition to Disease Glutathione Transferase - genetics Humans Liver Diseases, Alcoholic - genetics Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Other diseases. Semiology Pharmacology. Drug treatments Polymorphism, Genetic Risk Factors |
title | Meta‐analysis: glutathione‐S‐transferase allelic variants are associated with alcoholic liver disease |
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