Effect of mu-opioid receptor gene polymorphisms on heroin-induced subjective responses in a Chinese population

Background: Genetic factors that influence subjective responses to drug use (such as euphoria) contribute to the risk of addiction. mu-opioid receptor is the molecular target of heroin mediating its effects in both pain relief and euphoria. Methods: To evaluate the association of V-opioid receptor gene (OPRM1) variants with heroin-induced positive responses on first use, we studied 336 Chinese Han heroin addicts recruited in Shanghai and divided heroin addicts into two groups (positive vs. negative) according to the self-reporting feeling on first use. Association analyses with the genotypes and alleles in nine tagging single nucleotide polymorphisms (tSNPs) in OPRM1 with subjective responses were performed. Similar analysis with haplotypes of these tSNPs was also performed. Results: Allele frequencies of three tSNPs were significantly different between the positive and negative groups. They were rs696522 (odds ratio [OR] = 3.06,p =.0013),rs]381376(OR = 3.16,p =.0008),and rs3778151 (OR = 3.12,p =.0004). Such association remains after adjustment for demographic covariates and for multiple testing. The subjects with heroin-induced positive responses on first use consumed more drugs than the negative group (Mann-Whitney U = 224.0, Wilcoxon W = 16334.0,p <= 0001). Conclusions: Self-reported positive responses on first use of heroin were found to be associated with OPRM1. The findings suggest that heroin-induced positive responses are likely associated with more heroin consumption.