mu opioid receptor A118G polymorphism in association with striatal opioid neuropeptide gene expression in heroin abusers

作者：Drakenberg Katarina; Nikoshkov Andrej; Horvath Monika Cs; Fagergren Pernilla; Gharibyan Anna; Saarelainen Kati; Rahman Sadia; Nylander Ingrid; Bakalkin Georgy; Rajs Jovan; Keller Eva; Hurd Yasmin L^*

来源：Proceedings of the National Academy of Sciences, 2006, 103(20): 7883-7888.

DOI：10.1073/pnas.0600871103

• drug abuse
• dynorphin
• enkephalin
• mRNA

mu Opioid receptors are critical for heroin dependence, and A118G SNP of the mu opioid receptor gene (OPRM1) has been linked with heroin abuse. In our population of European Caucasians (n = 118), approximate to 90% of 118G allelic carriers were heroin users. Postmortem brain analyses showed the OPRM1 genotype associated with transcription, translation, and processing of the human striatal opioid neuropeptide system. Whereas down-regulation of preproenkephalin and preprodynorphin genes was evident in all heroin users, the effects were exaggerated in 118G subjects and were most prominent for preproenkephalin in the nucleus accumbens shell. Reduced opioid neuropeptide transcription was accompanied by increased dynorphin and enkephalin peptide concentrations exclusively in 118G heroin subjects, suggesting that the peptide processing is associated with the OPRM1 genotype. Abnormal gene expression related to peptide convertase and ubiquitin/proteosome regulation was also evident in heroin users. Taken together, alterations in opioid neuropeptide systems might underlie enhanced opiate abuse vulnerability apparent in 118G individuals.

• 出版日期2006-5-16