Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
Curr Neuropharmacol. 2011 Mar;9(1):133-6. doi: 10.2174/157015911795016994.
Disruption of circadian rhythms may be involved in the pathophysiology of psychiatric disorders, including drug addiction. Recently, we detected the significant association between prokineticin 2 receptor gene (PROKR2) and Japanese methamphetamine dependence patients. Also, prokineticin 2 (PK2) gene deficient mice showed reduced physiological and behavioral parameters, including circadian locomotor activity, circulating glucocorticoid, glucose levels and the expression of peripheral clock genes compared with WT mice. These evidences indicate that PK2 gene (PROK2) is a good candidate gene for the pathogenesis of methamphetamine dependence. To evaluate the association between PROK2 and methamphetamine dependence, we conducted a case-control study of Japanese samples (215 methamphetamine dependence and 232 controls) with four tagging SNPs selected by HapMap database. The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients. Written informed consent was obtained from each subject. This study was approved by the ethics committees at Fujita Health University, Nagoya University Graduate School of Medicine and each participating member of the Institute of the Japanese Genetics Initiative for Drug Abuse (JGIDA). We did not detect an association between PROK2 and Japanese methamphetamine dependence patients in allele/genotype-wise analysis, or the haplotype analysis. Our findings suggest that PROK2 does not play a major role in the pathophysiology of methamphetamine dependence in the Japanese population.
昼夜节律紊乱可能与包括药物成瘾在内的精神疾病的病理生理学有关。最近，我们发现促动力蛋白 2 受体基因（PROKR2）与日本甲基苯丙胺依赖患者之间存在显著关联。此外，与 WT 小鼠相比，促动力蛋白 2（PK2）基因缺失的小鼠表现出生理和行为参数的减少，包括昼夜节律性运动活动、循环糖皮质激素、血糖水平和外周时钟基因的表达。这些证据表明 PK2 基因（PROK2）是甲基苯丙胺依赖发病机制的候选基因。为了评估 PROK2 与甲基苯丙胺依赖之间的关联，我们对日本样本（215 例甲基苯丙胺依赖和 232 例对照）进行了病例对照研究，这些样本是通过 HapMap 数据库选择的四个标记 SNP。对照受试者的年龄和性别与甲基苯丙胺依赖患者无差异。每位受试者均获得书面知情同意。本研究得到了藤田保健大学、名古屋大学研究生院医学部和日本药物滥用遗传学倡议研究所（JGIDA）每个成员的伦理委员会的批准。在等位基因/基因型分析或单体型分析中，我们未发现 PROK2 与日本甲基苯丙胺依赖患者之间存在关联。我们的研究结果表明，PROK2 不会在日本人群中发挥主要作用甲基苯丙胺依赖的发病机制。
