Alpha4 and beta2 subunits of neuronal nicotinic acetylcholine receptor genes are not associated with methamphetamine-use disorder in the Japanese population.
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.
Kishi
Taro
T
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan. taroh@fujita-hu.ac.jp
Ikeda
Masashi
M
Kitajima
Tsuyoshi
T
Yamanouchi
Yoshio
Y
Kinoshita
Yoko
Y
Kawashima
Kunihiro
K
Inada
Toshiya
T
Harano
Mutsuo
M
Komiyama
Tokutaro
T
Hori
Toru
T
Yamada
Mitsuhiko
M
Iyo
Masaomi
M
Sora
Ichiro
I
Sekine
Yoshimoto
Y
Ozaki
Norio
N
Ujike
Hiroshi
H
Iwata
Nakao
N
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*
D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D021122:Protein Subunits; D011978:Receptors, Nicotinic; C436489:CHRNA2 protein, human