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 - 01-01-2008

Publication series

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

Fingerprint

Methamphetamine
Nicotinic Receptors
Nicotine
Genes
Cholinergic Receptors
Population
Single Nucleotide Polymorphism
Linkage Disequilibrium
Pharmaceutical Preparations
Psychotic Disorders
Substance-Related Disorders
Dopamine
Brain
Binding Sites
Gene
Testing

All Science Journal Classification (ASJC) codes

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

Cite this

Kishi, T., Ikeda, M., Kitajima, T., Yamanouchi, Y., Kinoshita, Y., Kawashima, K., ... 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
Kishi, Taro ; Ikeda, Masashi ; Kitajima, Tsuyoshi ; Yamanouchi, Yoshio ; Kinoshita, Yoko ; Kawashima, Kunihiro ; Inada, Toshiya ; Harano, Mutsuo ; Komiyama, Tokutaro ; Hori, Toru ; Yamada, Mitsuhiko ; Iyo, Masaomi ; Sora, Ichiro ; Sekine, Yoshimoto ; Ozaki, Norio ; Ujike, Hiroshi ; Iwata, Nakao. / Alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptor genes are not associated with methamphetamine-use disorder in the Japanese population. Drug Addiction: Research Frontiers and Treatment Advances. Blackwell Publishing Inc., 2008. pp. 70-82 (Annals of the New York Academy of Sciences).
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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.",
author = "Taro Kishi and Masashi Ikeda and Tsuyoshi Kitajima and Yoshio Yamanouchi and Yoko Kinoshita and Kunihiro Kawashima and Toshiya Inada and Mutsuo Harano and Tokutaro Komiyama and Toru Hori and Mitsuhiko Yamada and Masaomi Iyo and Ichiro Sora and Yoshimoto Sekine and Norio Ozaki and Hiroshi Ujike and Nakao Iwata",
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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. Annals of the New York Academy of Sciences, vol. 1139, Blackwell Publishing Inc., pp. 70-82. https://doi.org/10.1196/annals.1432.023

Alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptor genes are not associated with methamphetamine-use disorder in the Japanese population. / Kishi, Taro; Ikeda, Masashi; Kitajima, Tsuyoshi; Yamanouchi, Yoshio; Kinoshita, Yoko; Kawashima, Kunihiro; Inada, Toshiya; Harano, Mutsuo; Komiyama, Tokutaro; Hori, Toru; Yamada, Mitsuhiko; Iyo, Masaomi; Sora, Ichiro; Sekine, Yoshimoto; Ozaki, Norio; Ujike, Hiroshi; Iwata, Nakao.

Drug Addiction: Research Frontiers and Treatment Advances. Blackwell Publishing Inc., 2008. p. 70-82 (Annals of the New York Academy of Sciences; Vol. 1139).

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

TY - GEN

T1 - Alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptor genes are not associated with methamphetamine-use disorder in the Japanese population

AU - Kishi, Taro

AU - Ikeda, Masashi

AU - Kitajima, Tsuyoshi

AU - Yamanouchi, Yoshio

AU - Kinoshita, Yoko

AU - Kawashima, Kunihiro

AU - Inada, Toshiya

AU - Harano, Mutsuo

AU - Komiyama, Tokutaro

AU - Hori, Toru

AU - Yamada, Mitsuhiko

AU - Iyo, Masaomi

AU - Sora, Ichiro

AU - Sekine, Yoshimoto

AU - Ozaki, Norio

AU - Ujike, Hiroshi

AU - Iwata, Nakao

PY - 2008/1/1

Y1 - 2008/1/1

N2 - 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.

AB - 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.

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Kishi T, Ikeda M, Kitajima T, Yamanouchi Y, Kinoshita Y, Kawashima K et al. 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. Blackwell Publishing Inc. 2008. p. 70-82. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1432.023