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To identify patients who may be most responsive to naltrexone treatment, studies have examined the moderating effect of rs1799971, a single nucleotide polymorphism (SNP) that encodes a non\u2010synonymous substitution (Asn40Asp) in the mu\u2010opioid receptor gene, <jats:italic>OPRM1<\/jats:italic>. The aims of this study were to: (1) conduct a systematic review of randomized clinical trials (RCTs); (2) assess the bias of the available studies and gauge publication bias; and (3) meta\u2010analyze the interaction effect of the Asn40Asp SNP on the response to naltrexone treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched for placebo\u2010controlled RCTs that examined the effect of Asn40Asp on the response to naltrexone treatment of heavy drinking or AUD. We tested the hypothesis that the minor (Asp40) allele was associated with a greater reduction in five alcohol consumption measures (relapse to heavy drinking, abstinence, percentage of heavy drinking days, percentage of days abstinent and drinks per day) in naltrexone\u2010treated participants by meta\u2010analyzing the interaction effects using a random effects model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seven RCTs met the study criteria. Overall, risk of bias was low and we observed no evidence of publication bias. Of the five alcohol consumption outcomes considered, there was a nominally significant moderating effect of the Asn40Asp SNP only on drinks per day (<jats:italic>d<\/jats:italic>\u00a0=\u00a0\u22120.18, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.02). However, the effect was not significant when multiple comparisons were taken into account.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>From the evidence to date, it remains unclear whether rs1799971, the <jats:italic>OPRM1<\/jats:italic> Asn40Asp single nucleotide polymorphism, predicts naltrexone treatment response in individuals with alcohol use disorder or heavy drinking.<\/jats:p><\/jats:sec>","DOI":"10.1111\/add.14975","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T20:23:48Z","timestamp":1579638228000},"page":"1426-1437","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Systematic review and meta\u2010analysis of the moderating effect of rs1799971 in <i>OPRM1<\/i>, the mu\u2010opioid receptor gene, on response to naltrexone treatment of alcohol use disorder"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5137-9714","authenticated-orcid":false,"given":"Emily E.","family":"Hartwell","sequence":"first","affiliation":[{"name":"Mental Illness Research, Education and Clinical Center  Philadelphia PA, USA"},{"name":"Center for Studies of Addiction, Department of Psychiatry University of Pennsylvania Perelman School of Medicine  Philadelphia PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Feinn","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Frank H. Netter School of Medicine at Quinnipiac University  North Haven CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige E.","family":"Morris","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry University of Pennsylvania Perelman School of Medicine  Philadelphia PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Gelernter","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry, Genetics, and Neuroscience Yale University School of Medicine  and VA Connecticut Healthcare West Haven CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Krystal","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3091-8504","authenticated-orcid":false,"given":"Albert J.","family":"Arias","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Virginia Commonwealth University School of Medicine  Richmond VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Medical University of South Carolina  Charleston SC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismene","family":"Petrakis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralitza","family":"Gueorguieva","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"Schacht","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Medical University of South Carolina  Charleston SC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Oslin","sequence":"additional","affiliation":[{"name":"Mental Illness Research, Education and Clinical Center  Philadelphia PA, USA"},{"name":"Center for Studies of Addiction, Department of Psychiatry University of Pennsylvania Perelman School of Medicine  Philadelphia PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond F.","family":"Anton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Medical University of South Carolina  Charleston SC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-0450","authenticated-orcid":false,"given":"Henry R.","family":"Kranzler","sequence":"additional","affiliation":[{"name":"Mental Illness Research, Education and Clinical Center  Philadelphia PA, USA"},{"name":"Center for Studies of Addiction, Department of Psychiatry University of Pennsylvania Perelman School of Medicine  Philadelphia PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Center for Behavioral Health Statistics and Quality.2016National Survey on Drug Use and Health: Detailed Tables. 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