Association between opioid and dopamine receptor gene polymorphisms OPRM1rs1799971, DAT VNTR9-10 repeat allele, DRD1 rs4532 and DRD2 rs1799732 and alcohol dependence: an ethnicity oriented meta-analysis.

Abstract

We carried out a meta-analysis of four opioid and dopamine candidate gene polymorphisms having conflicting results in prior literature, namely OPRM1 rs1799971, DAT VNTR9-10 repeat, DRD1 rs4532 and DRD2 rs1799732, to clarify their association with alcohol dependence and further stratified results by ethnicity to analyze possible ethnicity-mediated effects. Inclusion criteria: case-control studies assessing the association between OPRM1 rs1799971, DAT VNTR9/10 repeat allele, DRD1 rs4532 and DRD2 rs1799732 with alcohol dependence, with sufficient data available to calculate the odds ratio (OR) within a 95% confidence interval. Exclusion criteria: studies of quantitative measures of alcohol consumption, response to medications or analyses of other markers in the candidate genes, studies without controls, animal studies and lack of genotyping data. Information sources were PubMed, Google Scholar and ScienceDirect databases, all of which were searched for articles published till 2021. Heterogeneity between studies and publication bias, subgroup analyses and sensitivity analyses were carried out. A total of 41 published studies were included in the current meta-analysis. For the OPRM1 gene, there was a statistically significant association in the Asian population with a pooled OR of 1.707 (95% CI, 1.32-2.20 P < 0.0001) and 1.618 (95% CI, 1.16-2.26 P = 0.005) in the additive and dominant genetic models. For DAT VNTR 9/10 repeat, a statistically significant association of the risk vs. common allele was observed in AD with a pooled OR of 1.104 (95% CI, 1.00-1.21 P = 0.046) in the allele model and the additive genetic model in the Caucasian population with pooled OR of 1.152 (95% CI, 1.01-1.31 P = 0.034). Results indicate that some of the effects may be ethnicity-specific. The meta-analysis has been registered in the CRD PROSPERO (CRD42023411576).