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 language | English |
|---|---|
| Title of host publication | Drug Addiction |
| Subtitle of host publication | Research Frontiers and Treatment Advances |
| Publisher | Blackwell Publishing Inc. |
| Pages | 70-82 |
| Number of pages | 13 |
| ISBN (Print) | 9781573317184 |
| DOIs | |
| Publication status | Published - 10-2008 |
Publication series
| Name | Annals of the New York Academy of Sciences |
|---|---|
| Volume | 1139 |
| ISSN (Print) | 0077-8923 |
| ISSN (Electronic) | 1749-6632 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science
Cite this
}
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 proceeding › Conference 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 - 2008/10
Y1 - 2008/10
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.
UR - http://www.scopus.com/inward/record.url?scp=53549124705&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=53549124705&partnerID=8YFLogxK
U2 - 10.1196/annals.1432.023
DO - 10.1196/annals.1432.023
M3 - Conference contribution
C2 - 18991851
AN - SCOPUS:53549124705
SN - 9781573317184
T3 - Annals of the New York Academy of Sciences
SP - 70
EP - 82
BT - Drug Addiction
PB - Blackwell Publishing Inc.
ER -