title: Alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptor genes are not associated with methamphetamine-use disorder in the Japanese population.
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.
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan. taroh@fujita-hu.ac.jp
authors.forename: Taro
authors.initials: T
authors.lastname: Kishi
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kitajima
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamanouchi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Kawashima
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Harano
authors.forename: Tokutaro
authors.initials: T
authors.lastname: Komiyama
authors.forename: Toru
authors.initials: T
authors.lastname: Hori
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D021122:Protein Subunits / Q000235:genetics*; D011605:Psychoses, Substance-Induced; D011978:Receptors, Nicotinic / Q000235:genetics*
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D021122:Protein Subunits; D011978:Receptors, Nicotinic; C436489:CHRNA2 protein, human