Opioid Exposure is Associated with Aberrant DNA Methylation of OPRM1 Promoter Region in a Chinese Han Population

The μ-opioid receptor (OPRM1) plays an important role in opiate addiction. The OPRM1 gene promoter showed hypermethylation in lymphocytes of opiate addicts as well as opioid medications users, while the methylation status displayed ethnic diversity. The purpose of the study was to investigate the methylation pattern of OPRM1 promoter in the Han Chinese population. We analyzed 22 CpG sites located in OPRM1 promoter in 186 former opiate addicts (94 males and 92 females) and 184 healthy controls (102 males and 82 females). The + 126 CpG site was significantly hypermethylated in the former heroin addicts compared with controls (13.67% versus 8.39%, \(P = 3.78 \times 10^{ - 9}\), corrected for 36 tests). Six CpG sites were significantly associated with opioid exposure, including the most significant +126 CpG site (opiate addicts 13.57%, control 8.39%, \(P = 9.19 \times 10^{ - 12}\), corrected for 36 tests), while the +23 GpG site was the only hypomethylated one in former opiate addicts compared with controls (P = 0.0023 after Bonferroni correction). Our results supported that opioid exposure was associated with methylation status of OPRM1 promoter and showed ethnic dependence.