Hypermethylation in the promoter region of the ADRA1A gene is associated with opioid use disorder in Han Chinese

Abstract

Opioid use disorder is a chronic brain disease influenced by genetic and epigenetic factors, accounting for approximately 50% of the liability. Adrenergic signaling is involved in opioid use disorder. To demonstrate the associations between methylation alterations in the alpha-1-adrenergic receptor (ADRA1A) gene and opioid use disorder, in the present study, we first examined and compared the methylation levels of 97 CpG sites in the promoter region of the ADRA1A gene in the peripheral blood in 120 patients with heroin use disorder and 111 healthy controls. Correlations between methylation levels and duration of heroin/methadone use were then analyzed. Finally, the predicted binding transcription factors (TFs) and their target sequences in the promoter region of the ADRA1A gene, which include the selected CpG sites, were screened in the JASPAR database. Our results demonstrated that hypermethylation in the promoter region of the ADRA1A gene in the blood was associated with opioid use disorder. Correlations between methylation levels of several CpG sites and duration of heroin/methadone use were observed. TFs TFAP2A and RUNX1 were predicted to bind to the target sequences, which include the CpG sites selected in the current study, in the promoter region of the ADRA1A gene. Our findings further extend the associations between methylation alterations in the ADRA1A gene and opioid use disorder potentially through mechanisms of gene expression regulations in the ADRA1A gene.