The impact of OPRM1 single nucleotide polymorphisms and haplotypes on the alcohol use disorder

Abstract

Background. In modern society, alcohol use disorder (AUD) is a common problem, which is often accompanied by somatic and psychiatric disorders and social problems. Despite widely conducted research, there is no effective treatment for AUD. About 50% of the risk for AUD is inherited. One of the most researched single nucleotide polymorphism (SNP) in AUD pathogenesis is OPRM1 rs1799971. However, the results of this SNP were inconsistent, both A and G alleles were demonstrated to be associated with the AUD. Other SNPs in OPRM1 gene were related with other addiction disorders and may play role in AUD. Therefore, we aimed to study the impact of SNPs rs7758009, rs1074287, rs1799971, rs3778150, rs9479757, rs648893, rs671531, rs1918760, rs2272381 and their haplotypes on the risk for AUD Methods. The study included 838 participants recruited from local community (N=726) and addictive disorders treatment center (N=112). The risk of AUD was evaluated by Alcohol Use Disorder Identification Test (AUDIT). Impulsivity was measured by Barrat Impulsiviness Scale-11 (BIS-11). Only those samples which were at least half genotyped were included in the prelimany haplotype analysis. Associations of separate SNPs with AUDIT and BIS-11 scores were evaluated by ANOVA. Haplotypes were established by Haplowiev sofware. Haplotype analysis was conducted using haplo.stats package in R software. Results. Rs1799971 G allele and rs7758009 C allele were associated to AUDIT score (p<0.01). Rs1799971 G allele was associated to BIS. Three haplotype blocks were established (rs7758009-rs1799971, rs1799971-rs3778150, rs648893-rs671531). AUDIT score was associated with haplotypes C-G and T-A in haploblock rs7758009-rs1799971 (p values < 0.05 and <0.01 accordingly and haplotypes G-T and A-T in haploblock rs1799971-rs3778150. BIS-11 scores were associated with haplotypes G-T and A-T in haploblock rs1799971(p values <0.05). Conclusions. The effect of separate SNP could be influenced by interaction with other SNPs. We plan on genotyping the remaining samples for a better evaluation of haplotypes impact on AUD. Both BIS-11 and AUDIT scores were related to rs1799971 SNP and to the haplotypes in haploblock rs1799971-rs3778150. These results suggest the need of subsequent analysis performing structural equation modeling to evaluate direct or indirect effect of SNPs and haplotypes on the risk of AUD. Better understanding of AUD pathogenesis could benefit the development of more effective treatment methods.