Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin.

Human mu-opioid receptor (OPRM1) is the major site for the analgesic action of most opioid drugs such as morphine, methadone and heroin. It was previously reported that a single nucleotide polymorphism (SNP) in exon1 (c.118A-->G) of OPRM1 might modestly alter the affinity in beta-endorphin-Mu interaction. Using denaturing high performance liquid chromatography (DHPLC) the complete coding region of the OPRM1 gene was screened for SNPs in Han-Chinese heroin addicts and normal control. Three novel SNPs were detected, one in exon3, one in intron3 and one in the 3' untranslated region. The SNP c.118A-->G reportedly altered the interaction of Mu receptor with opioid had no statistically significant correlation with heroin addition in Han Chinese. However, addicted subjects with the SNP in intron2 (IVS2 +31G-->A) tended to show much higher heroin intake dosages than those without this SNP. We also observed that individuals carrying both SNP c.118A-->G and IVS2 +31G-->A consumed relatively more drugs compared to other addicts. Thus our study further highlights the importance of studing the various regions of the mu opioid receptor gene, coding as well as non-coding, for genetic markers that may be linked to, or directly contribute to opioid drug-seeking behavior. Copyright 2002 Wiley-Liss, Inc.