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Gene polymorphisms of the mu opioid receptor in methamphetamine abusers

Soichiro Ide1, Hideaki Kobayashi, Keiko Tanaka

  • 1Department of Molecular Psychiatry, Tokyo Institute of Psychiatry, Japan.

Annals of the New York Academy of Sciences
|November 16, 2004
PubMed

Insights

Genetic variations in the mu-opioid receptor gene (OPRM) were studied in relation to methamphetamine (MAP) dependence and psychosis. The A118G OPRM variation showed a significant association with MAP psychosis developing within three years.

Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • The opioid system influences motivational effects in drug addiction, potentially via dopamine-independent pathways.
  • Investigating genetic variations in the mu-opioid receptor gene (OPRM) is crucial for understanding methamphetamine (MAP) dependence and psychosis.
  • Allelic frequencies of OPRM variations, such as A118G, differ across ethnic populations.

Purpose of the Study:

  • To investigate the associations between OPRM gene variations and methamphetamine (MAP) dependence and psychosis.
  • To identify novel polymorphisms in the OPRM gene, particularly in regulatory regions.
  • To compare OPRM gene polymorphism frequencies between Japanese and other ethnic groups in the context of MAP abuse.

Main Methods:

  • Genotyping of OPRM gene variations, including single nucleotide polymorphisms (SNPs) and dinucleotide repeats.
  • Analysis of allelic and genotype frequencies in control subjects and MAP abusers.
  • Comparison of OPRM gene polymorphism data between Japanese, Caucasian, and African-American populations.

Main Results:

  • Novel OPRM polymorphisms were identified in intron 1 and the 5' untranslated region (5'UTR).
  • Significant differences in OPRM polymorphisms were observed in the Japanese population compared to Caucasian and African-American populations, especially in the 5' regulatory region.
  • No significant differences in genotype or allele frequencies were found for most OPRM variations between controls and MAP abusers.
  • A significant association was found between the OPRM A118G variation and MAP psychosis with a latency of less than three years.

Conclusions:

  • While most OPRM variations did not show a direct link to MAP dependence, the A118G polymorphism is significantly associated with early-onset MAP psychosis.
  • Further research is warranted to elucidate the precise role of OPRM variations in MAP dependence and the development of psychosis.
  • Population-specific differences in OPRM gene polymorphisms may influence susceptibility to MAP-related disorders.

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