Abstract
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.
Highlights
Disruption of circadian rhythms may be involved in the pathophysiology of psychiatric disorders, including drug addiction [1,2,3,4,5,6,7]
We reasoned that PROK2 may not play an important role in the pathophysiology of METH dependence and METH-induced psychosis in the Japanese population
We detected the associations between prokineticin 2 receptor (PROKR2) and mood disorders including MDD and BP and METH dependence and METH-induced psychosis in the Japanese population [11, 21]
Summary
Disruption of circadian rhythms may be involved in the pathophysiology of psychiatric disorders, including drug addiction [1,2,3,4,5,6,7]. Several animal studies have shown that methamphetamine increased expression of circadian clock molecule genes such as Per, Per, Bmal, and Npas in the brain [8,9,10]. We detected the significant association between prokineticin 2 receptor gene (PROKR2) and Japanese methamphetamine dependence patients [11]. The 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 [12,13,14,15]. The expression of PK2 gene in SCN was activated by the Clock/Bmal complex,
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