Genomic factors associated with substance use disorder relapse: A critical review

Abstract

Several genetic and epigenetic factors contribute to the elevated substance use disorder (SUD) relapse vulnerability, yet a comprehensive investigation into these factors is lacking. This review aims to delve into current literature to highlight key genomic factors associated with SUD relapse.Focusing on genetic predisposition and epigenetic modifications the review synthesized research findings of several genetic polymorphisms, histone modifications and DNA methylation patterns contributing to the initiation of SUD and the elevated relapse susceptibility. Notably, specific gene polymorphisms, such as Dopamine Receptor D2 gene (DRD2), Gamma-Aminobutyric Acid Receptor Alpha gene (GABRA2), Catechol-O-methyltransferase (COMT) gene, Dopamine Transporter (DAT1) gene and others were identified to be connected to various patterns of SUD relapse. Furthermore, SUD initiation and relapse has been shown to be influenced by epigenetics. Specifically, CpG hypermethylation has been associated with severe alcohol use disorder in the 5′ untranslated region of the Bladder Cancer Associated Protein gene (BLCAP) and the upstream region of the Active BCR Related gene (ABR). Co-users of cannabis and tobacco showed notable variations in CpG site methylation, especially at the Aryl Hydrocarbon Receptor Repressor (AHRR), and factor II receptor-like 3 gene sites (F2RL3).In conclusion, there is good evidence of certain associations between genomic factors and relapse to SUD. However, further research is needed to ascertain causality effects of these factors and develop novel interventions for effective treatment and relapse prevention.