Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Genes Brain Behav. 2011 Apr;10(3):257-63. doi: 10.1111/j.1601-183X.2010.00661.x. Epub 2010 Nov 22.
Several lines of evidence suggest that alterations in circadian rhythms might be associated with the pathophysiology of psychiatric disorders such as schizophrenia and bipolar disorder (BP). A recent study reported that SIRT1 is a molecule that plays an important role in the circadian clock system. Therefore, to evaluate the association among the SIRT1 gene, schizophrenia and BP, we conducted a case-control study of Japanese population samples (1158 schizophrenia patients, 1008 BP patients and 2127 controls) with four tagging SNPs (rs12778366, rs2273773, rs4746720 and rs10997875) in the SIRT1 gene. Marker-trait association analysis was used to evaluate the allele and the genotype association with the χ(2) test, and haplotype association analysis was evaluated with a likelihood ratio test. We showed an association between rs4746720 in the SIRT1 gene and schizophrenia in the allele and the genotype analysis. However, the significance of these associations did not survive after Bonferroni's correction for multiple testing. On the other hand, the SIRT1 gene was associated with Japanese schizophrenia in a haplotype-wise analysis (global P(all markers) = 4.89 × 10(-15)). Also, four tagging SNPs in the SIRT1 gene were not associated with BP. In conclusion, the SIRT1 gene may play an important role in the pathophysiology of schizophrenia in the Japanese population.
有几条证据表明，昼夜节律的改变可能与精神疾病的病理生理学有关，如精神分裂症和双相情感障碍 (BP)。最近的一项研究报告称，SIRT1 是一种在昼夜节律钟系统中起重要作用的分子。因此，为了评估 SIRT1 基因、精神分裂症和 BP 之间的关联，我们对日本人群样本（1158 例精神分裂症患者、1008 例 BP 患者和 2127 例对照）进行了一项病例对照研究，研究中包含了 SIRT1 基因中的四个标记 SNP（rs12778366、rs2273773、rs4746720 和 rs10997875）。使用 χ(2)检验进行标记-性状关联分析，以评估等位基因和基因型与疾病的关联，使用似然比检验进行单体型关联分析。我们发现 SIRT1 基因中的 rs4746720 与精神分裂症的等位基因和基因型分析有关。然而，这些关联在经过 Bonferroni 多重检验校正后并不显著。另一方面，SIRT1 基因与日本精神分裂症在单体型分析中有关（所有标记的全局 P(all markers) = 4.89 × 10(-15)）。此外，SIRT1 基因中的四个标记 SNP 与 BP 无关。总之，SIRT1 基因可能在日本人群精神分裂症的病理生理学中起重要作用。
