Alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptor genes are not associated with methamphetamine-use disorder in the Japanese population

Taro Kishi, Masashi Ikeda, Tsuyoshi Kitajima, Yoshio Yamanouchi, Yoko Kinoshita, Kunihiro Kawashima, Toshiya Inada, Mutsuo Harano, Tokutaro Komiyama, Toru Hori, Mitsuhiko Yamada, Masaomi Iyo, Ichiro Sora, Yoshimoto Sekine, Norio Ozaki, Hiroshi Ujike, Nakao Iwata

Research output: Chapter in Book/Report/Conference proceedingConference contribution

14 Citations (Scopus)

Abstract

The mesolimbic system is thought to be involved in the reinforcing action of many addictive drugs and the release of dopamine modulated by neuronal nicotine cholinergic receptors (nAChRs). Several investigations suggested that nAChRs on dopaminergic terminals play an important role in the development of some long-lasting adaptations associated with drug abuse. A majority of high-affinity nicotine binding sites in the brain have been showed in heteropentameric alpha4 (alpha4) and beta2 subunit (beta2) of nAChRs. Therefore, we conducted a genetic association analysis of the alpha4 gene (CHRNA4) and beta2 gene (CHRNB2) with methamphetamine (METH)-use disorder (191 cases and 753 controls). We first evaluated the linkage disequilibrium (LD) structure of these genes and selected 7 and 5 tagging SNPs (tag SNPs) on CHRNA4 and CHRNB2, respectively. Some tag SNPs were significantly associated with total METH-use disorder and METH-induced psychosis; however, these associations were no longer statistically significant after Bonferroni's correction for multiple testing. In conclusion, our results suggest that neither CHRNA4 nor CHRNB2 plays a major role in Japanese METH-use disorder.

Original languageEnglish
Title of host publicationDrug Addiction
Subtitle of host publicationResearch Frontiers and Treatment Advances
PublisherBlackwell Publishing Inc.
Pages70-82
Number of pages13
ISBN (Print)9781573317184
DOIs
Publication statusPublished - 10-2008

Publication series

NameAnnals of the New York Academy of Sciences
Volume1139
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Kishi, T., Ikeda, M., Kitajima, T., Yamanouchi, Y., Kinoshita, Y., Kawashima, K., Inada, T., Harano, M., Komiyama, T., Hori, T., Yamada, M., Iyo, M., Sora, I., Sekine, Y., Ozaki, N., Ujike, H., & Iwata, N. (2008). Alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptor genes are not associated with methamphetamine-use disorder in the Japanese population. In Drug Addiction: Research Frontiers and Treatment Advances (pp. 70-82). (Annals of the New York Academy of Sciences; Vol. 1139). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1432.023