The adenosine A2A receptor is associated with methamphetamine dependence/psychosis in the Japanese population.
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.
Kobayashi
Hideaki
H
Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Ujike
Hiroshi
H
Iwata
Nakao
N
Inada
Toshiya
T
Yamada
Mitsuhiko
M
Sekine
Yoshimoto
Y
Uchimura
Naohisa
N
Iyo
Masaomi
M
Ozaki
Norio
N
Itokawa
Masanari
M
Sora
Ichiro
I
D000328:Adult; D000483:Alleles; D019969:Amphetamine-Related Disorders / Q000235:genetics*; D044466:Asian People / Q000235:genetics* / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011605:Psychoses, Substance-Induced / Q000235:genetics*; D043705:Receptor, Adenosine A2A / Q000235:genetics*; D012727:Sex Characteristics
D043705:Receptor, Adenosine A2A
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