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Effect of μ-Opioid Receptor Gene Polymorphisms on Heroin-Induced Subjective Responses in a Chinese Population

  • Author Footnotes
    1 DZ and CS contributed equally to this work.
    Dandan Zhang
    Footnotes
    1 DZ and CS contributed equally to this work.
    Affiliations
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana
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  • Author Footnotes
    1 DZ and CS contributed equally to this work.
    Chunhong Shao
    Footnotes
    1 DZ and CS contributed equally to this work.
    Affiliations
    Huashan Hospital, Fudan University, West Lafayette, Indiana
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  • Minhua Shao
    Affiliations
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana
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  • Pengrong Yan
    Affiliations
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana
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  • Yi Wang
    Affiliations
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana
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  • Yixiao Liu
    Affiliations
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana
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  • Wenhong Liu
    Affiliations
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana
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  • Tong Lin
    Affiliations
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana
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  • Yuying Xie
    Affiliations
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana
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  • Yingnan Zhao
    Affiliations
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana
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  • Daru Lu
    Affiliations
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana

    Huashan Hospital, Fudan University, West Lafayette, Indiana

    Department of Biochemistry, Purdue University, West Lafayette, Indiana

    CAS-MPG Partner Institute of Computational Biology, SIBS, CAS, Shanghai, China.
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  • Yifeng Li
    Affiliations
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana

    Department of Biochemistry, Purdue University, West Lafayette, Indiana
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  • Li Jin
    Correspondence
    Address reprint requests to Li Jin, Ph.D., School of Life Sciences, Fudan University, 220 Handan Road., Shanghai, 200443, China.
    Affiliations
    MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, West Lafayette, Indiana

    CAS-MPG Partner Institute of Computational Biology, SIBS, CAS, Shanghai, China.
    Search for articles by this author
  • Author Footnotes
    1 DZ and CS contributed equally to this work.
Published:December 11, 2006DOI:https://doi.org/10.1016/j.biopsych.2006.07.012

      Background

      Genetic factors that influence subjective responses to drug use (such as euphoria) contribute to the risk of addiction. μ-opioid receptor is the molecular target of heroin mediating its effects in both pain relief and euphoria.

      Methods

      To evaluate the association of μ-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), rs1381376 (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.

      Key Words

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