TY - JOUR
T1 - The adenosine A2A receptor is associated with methamphetamine dependence/psychosis in the Japanese population
AU - Kobayashi, Hideaki
AU - Ujike, Hiroshi
AU - Iwata, Nakao
AU - Inada, Toshiya
AU - Yamada, Mitsuhiko
AU - Sekine, Yoshimoto
AU - Uchimura, Naohisa
AU - Iyo, Masaomi
AU - Ozaki, Norio
AU - Itokawa, Masanari
AU - Sora, Ichiro
N1 - Funding Information:
We thank all the subjects who participated in this study. This study was supported in part by a Grant-in-Aid for Health and Labour Science Research (Research on Pharmaceutical and Medical Safety) from the Ministry of Health, Labour and Welfare of Japan; and by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2010/8/30
Y1 - 2010/8/30
N2 - Background: Several lines of evidence suggest that the dopaminergic nervous system contributes to methamphetamine (METH) dependence, and there is increasing evidence of antagonistic interactions between dopamine and adenosine receptors. We therefore hypothesized that variations in the A2A adenosine receptor (ADORA2A) gene modify genetic susceptibility to METH dependence/psychosis.Methods: We first analyzed variations in the exons and exon-intron boundaries of the ADORA2A gene in METH dependent/psychotic patients. Then an association analysis between these single nucleotide polymorphisms and METH dependence/psychosis was performed using a total of 171 METH dependent/psychotic patients and 229 controls.Results: We found 6 variations, of which one single nucleotide polymorphism (SNP) was novel. Significant associations were observed between the allelic and genotypic frequencies of the Exon2+751 (rs5751876) SNP and METH dependence/psychosis. These associations were observed especially in females. In the clinical feature analyses, significant associations were observed between the SNP and the patient subgroup using METH alone (i.e., without concomitant use of other substances of abuse).Conclusions: These results suggest that the ADORA2A gene could be a vulnerability factor for METH dependence/psychosis, especially in females and/or in patients using only METH.
AB - Background: Several lines of evidence suggest that the dopaminergic nervous system contributes to methamphetamine (METH) dependence, and there is increasing evidence of antagonistic interactions between dopamine and adenosine receptors. We therefore hypothesized that variations in the A2A adenosine receptor (ADORA2A) gene modify genetic susceptibility to METH dependence/psychosis.Methods: We first analyzed variations in the exons and exon-intron boundaries of the ADORA2A gene in METH dependent/psychotic patients. Then an association analysis between these single nucleotide polymorphisms and METH dependence/psychosis was performed using a total of 171 METH dependent/psychotic patients and 229 controls.Results: We found 6 variations, of which one single nucleotide polymorphism (SNP) was novel. Significant associations were observed between the allelic and genotypic frequencies of the Exon2+751 (rs5751876) SNP and METH dependence/psychosis. These associations were observed especially in females. In the clinical feature analyses, significant associations were observed between the SNP and the patient subgroup using METH alone (i.e., without concomitant use of other substances of abuse).Conclusions: These results suggest that the ADORA2A gene could be a vulnerability factor for METH dependence/psychosis, especially in females and/or in patients using only METH.
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U2 - 10.1186/1744-9081-6-50
DO - 10.1186/1744-9081-6-50
M3 - Article
C2 - 20799992
AN - SCOPUS:77956464341
SN - 1744-9081
VL - 6
JO - Behavioral and Brain Functions
JF - Behavioral and Brain Functions
M1 - 50
ER -