Association Analysis of the Adenosine A1 Receptor Gene Polymorphisms in Patients with Methamphetamine Dependence/Psychosis

>      Kobayashi; Hiroshi      Ujike; Nakao      Iwata; Toshiya      Inada; Mitsuhiko      Yamada; Yoshimoto      Sekine; Naohisa      Uchimura; Masaomi      Iyo; Norio      Ozaki; Masanari      Itokawa; Ichiro      Sora

Abstract

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 in METH abusers. We therefore hypothesized that variations in the A1 adenosine receptor (ADORA1) gene modify genetic susceptibility to METH dependence/psychosis. In this study, we identified 7 single nucleotide polymorphisms (SNPs) in exons and exon-intron boundaries of the ADORA1 gene in a Japanese population. A total of 171 patients and 229 controls were used for an association analysis between these SNPs and METH dependence/psychosis. No significant differences were observed in either the genotypic or allelic frequencies between METH dependent/psychotic patients and controls. A global test of differentiation among samples based on haplotype frequencies showed no significant association. In the clinical feature analyses, no significant associations were observed among latency of psychosis, prognosis of psychosis, and spontaneous relapse. These results suggest that the ADORA1 gene variants may make little or no contribution to vulnerability to METH dependence/psychosis.

Keywords: Single nucleotide polymorphism, SNP, variation, human, Japanese, MAP, abuse, dopamine, adenosinergic function, dopaminergic system