Abstract
Several investigations suggested abnormalities in circadian rhythms are related to the pathophysiology of psychiatric disorders, including drug addiction. Recently, orphan nuclear receptor rev-erb alpha and glycogen synthase kinase-3 β (GSK-3β) were shown to be important circadian components. In addition, the orphan nuclear receptor rev-erb alpha is a key negative feedback regulator of the circadian clock. These evidences indicate that rev-erb alpha gene (NR1D1) is a good candidate gene for the pathogenesis of methamphetamine dependence. To evaluate the association between NR1D1 and methamphetamine dependence, we conducted a case-control study of Japanese samples (215 methamphetamine dependence and 232 controls) with three tagging SNPs selected by HapMap database. 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 NR1D1 and Japanese methamphetamine dependence patients in allele/genotype-wise analysis, or the haplotype analysis. Our findings suggest that NR1D1 does not play a major role in the pathophysiology of methamphetamine dependence in the Japanese population.
Highlights
Several investigation suggest that abnormalities in circadian rhythms may be involved in the pathophysiology of psychiatric disorders, including drug addiction [1,2,3]
We did not detect between all tagging SNPs and METH dependence in the Japanese population in the allele /genotype-wise (Table 1) or haplotype-wise analysis (P haplotype= 0.775)
We found no association between four tagging SNPs and METH-induced psychosis patients in the allele /genotypewise (Table 1) or haplotype-wise analysis (P haplotype= 0.699)
Summary
Several investigation suggest that abnormalities in circadian rhythms may be involved in the pathophysiology of psychiatric disorders, including drug addiction [1,2,3]. The evidence for this relation is discussed in more detail in our previous papers and a review by Barnard and Nolan [4,5,6,7]. Yin et al showed that Rev-erb alpha is a target of GSK-3 kinase activity, needed to mediate this effect to regulate circadian rhythms [13]. These evidences indicate that rev-erb alpha gene (NR1D1) is a good candidate gene for the pathogenesis of methamphetamine dependence
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