Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
Curr Neuropharmacol. 2011 Mar;9(1):137-42. doi: 10.2174/157015911795016958.
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.
有几条证据表明多巴胺能神经系统与甲基苯丙胺(METH)成瘾有关,越来越多的证据表明在 METH 滥用者中,多巴胺和腺苷受体之间存在拮抗相互作用。因此,我们假设 A1 腺苷受体(ADORA1)基因的变异可以改变对 METH 依赖/精神病的遗传易感性。在这项研究中,我们在日本人群中鉴定了 ADORA1 基因外显子和外显子-内含子边界的 7 个单核苷酸多态性(SNP)。共使用 171 名患者和 229 名对照对这些 SNP 与 METH 依赖/精神病之间的关联进行了分析。在 METH 依赖/精神病患者和对照组之间,无论是基因型还是等位基因频率都没有观察到显著差异。基于单倍型频率的样本分化全局检验未显示出显著相关性。在临床特征分析中,未观察到精神病潜伏期、精神病预后和自发复发之间存在显著关联。这些结果表明,ADORA1 基因变异可能对 METH 依赖/精神病的易感性贡献很小或没有。