Abstract for presentation at 11th International Congress of Human Genetics

Association of μ-opioid receptor gene polymorphism A118G with alcohol dependence in a Japanese population

  • Daisuke Nishizawa, Unit of Human Biology and Genetics, Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan
  • Wenhua Han, Division of Psychobiology, Tokyo Institute of Psychiatry, Tokyo, Japan
  • Junko Hasegawa, Division of Psychobiology, Tokyo Institute of Psychiatry, Tokyo, Japan
  • Takafumi Ishida, Unit of Human Biology and Genetics, Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan
  • Yukio Numata, Koutokukai Sato Hospital Group, Yamagata, Japan
  • Tadahiro Sato, Koutokukai Sato Hospital Group, Yamagata, Japan
  • Atsuko Kawai, Koutokukai Sato Hospital Group, Yamagata, Japan
  • Kazutaka Ikeda, Division of Psychobiology, Tokyo Institute of Psychiatry, Tokyo, Japan

    • Purpose: Ethanol is considered to activate the brain reward system by increasing the release of an endogenous opioid receptor ligand, β-endorphin. The polymorphism A118G in the μ-opioid receptor gene (OPRM1) causes the amino acid change Asn40Asp and has been reported to affect the affinity of the ligand for the receptor. The association of this polymorphism with the vulnerability to alcohol dependence has been studied in many populations, but not in Japanese. In the present study, we compared the frequencies of the polymorphism OPRM1 A118G between the patients with alcohol dependence and healthy control subjects to investigate that association in a Japanese population. To better understand the genetic factors that would contribute to the prediction of the risk for alcohol dependence, we also genotyped a polymorphism, G1510A, in the acetaldehyde dehydrogenase 2 gene (ALDH2), in which the A allele causes poor metabolism of acetaldehyde, a major metabolite of alcohol.
    Methods: The peripheral blood of the patient and control subjects living in a Japanese provincial prefecture, were collected and the genomic DNAs were extracted. For genotyping the polymorphism OPRM1 A118G, allele-specific PCR using primers whose 3’ ends were specified in detecting the A or G allele and direct sequencing were performed. For genotyping the ALDH2 G1510A, Masscode(TM)system (QIAGEN Genomics, Inc.) using allele-specific reverse primers in the 2nd PCR after the 1st PCR by external primers was adopted.
    Results: None of the distributions of genotypes significantly deviated from the Hardy-Weinberg Equilibrium. There was a significant association between the genotypes containing the OPRM1 118G allele and alcohol dependence. Moreover, the ALDH2 1510G was significantly associated with alcohol dependence.
    Conclusions: Our results suggest that the polymorphism OPRM1 118G in addition to ALDH2 1510G would probably be one of the risk factors for alcohol dependence in Japanese.

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