Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
J Affect Disord. 2010 Oct;126(1-2):167-73. doi: 10.1016/j.jad.2010.04.003. Epub 2010 May 7.
Many studies including our previous ones as to PROKR2 and CLOCK have suggested that circadian genes may be involved in the mechanisms of mood disorders and their treatment responses. Also several recent investigations have reported that SIRT1 plays an important role in the circadian system as conventional circadian clock genes, and also have some relation to dopaminergic metabolism. So we considered the SIRT1 gene to be a good candidate gene for the pathophysiology for MDD and SSRI responses in MDD, and conducted a case-control study using four tagging SNPs (450 MDD patients, including 261 patients treated by SSRIs and 766 controls).
The MDD patients in this study had scores of 12 or higher on the 17 items of the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D). We defined a clinical response as a decrease of more than 50% in baseline SIGH-D within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Marker-trait association analysis was used to evaluate allele and genotype association with the chi-square test, and haplotype association analysis was evaluated with a likelihood ratio test.
We found an association between rs10997875 in SIRT1 gene and MDD in the allele/genotype analysis. In addition, this significance of these associations survived Bonferroni correction. However, we did not find any association between SIRT1 gene and SSRI therapeutic response in MDD in the allele/genotype analysis or haplotype analysis.
A replication study using larger samples may be required for conclusive results, since our sample size was small.
Our results suggest that rs10997875 in SIRT1 gene may play a role in the pathophysiology of MDD in the Japanese population.
包括我们之前的 PROKR2 和 CLOCK 研究在内的许多研究表明，生物钟基因可能与心境障碍的发病机制及其治疗反应有关。最近的几项研究还表明，SIRT1 作为传统生物钟基因在生物钟系统中发挥重要作用，并且与多巴胺代谢也有一定的关系。因此，我们认为 SIRT1 基因是 MDD 发病机制和 MDD 中 SSRI 反应的一个很好的候选基因，并使用四个标记 SNP（450 名 MDD 患者，包括 261 名接受 SSRI 治疗的患者和 766 名对照）进行了病例对照研究。
本研究中的 MDD 患者 SIGH-D 的 17 项总分达到 12 或更高。我们将临床反应定义为 8 周内基线 SIGH-D 评分下降 50%以上，临床缓解定义为 8 周时 SIGH-D 评分低于 7。采用卡方检验进行标记-性状关联分析，采用似然比检验进行单体型关联分析。
我们发现 SIRT1 基因中的 rs10997875 与 MDD 的等位基因/基因型分析存在关联。此外，这些关联的显著性在经过 Bonferroni 校正后仍然存在。然而，我们在 MDD 的等位基因/基因型分析或单体型分析中均未发现 SIRT1 基因与 SSRI 治疗反应之间存在任何关联。
由于我们的样本量较小，可能需要更大的样本量进行复制研究，以得出明确的结论。
我们的结果表明，SIRT1 基因中的 rs10997875 可能在日本人群的 MDD 发病机制中起作用。
