Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Neuromolecular Med. 2010 Sep;12(3):237-42. doi: 10.1007/s12017-009-8105-y. Epub 2009 Nov 24.
Several recent investigations reported that the serotonin 2A receptor gene (HTR2A) was associated with selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder. There have also been two reported association analyses of HTR2A with SSRI response in Japanese MDD patients, but the results were rather inconsistent and both studies had the problem of small sample sizes. Therefore, we conducted a replication association study using a sample larger than those in the two original Japanese studies (265 MDD patients), and found that four SNPs, two functional SNPs (-A1438G: rs6311 and T102C: rs6313) and two SNPs (rs7997012 and rs1928040) in HTR2A, were associated with the therapeutic response to SSRIs. HTR2A was associated with the therapeutic response SSRIs in Japanese MDD patients in a haplotype-wise analysis (P(all markers) = 0.0136), and a significant association between rs1928040 in HTR2A and SSRI response was detected in MDD (P(allele-wise analysis) = 0.0252). However, this significance disappeared after Bonferroni correction (P(allele-wise analysis) = 0.101). In conclusion, we suggest that HTR2A may play an important role in the pathophysiology of the therapeutic response to SSRIs in Japanese MDD patients. However, it will be important to replicate and confirm these findings in other independent studies using large samples.
几项最近的研究报告称，5-羟色胺 2A 受体基因（HTR2A）与选择性 5-羟色胺再摄取抑制剂（SSRIs）在重度抑郁症中有关。也有两项关于 HTR2A 与日本 MDD 患者 SSRIs 反应的关联分析报告，但结果相当不一致，而且两项研究都存在样本量小的问题。因此，我们进行了一项更大规模的复制关联研究（样本量大于两项原始日本研究），发现 HTR2A 中的四个 SNP，两个功能性 SNP（-A1438G：rs6311 和 T102C：rs6313）和两个 SNP（rs7997012 和 rs1928040）与 SSRIs 的治疗反应有关。在 HTR2A 的单体型分析中，HTR2A 与日本 MDD 患者 SSRIs 的治疗反应相关（P(all markers) = 0.0136），并且在 MDD 中检测到 HTR2A 中 rs1928040 与 SSRIs 反应之间存在显著关联（P(allele-wise analysis) = 0.0252）。然而，经过 Bonferroni 校正后，这种显著性消失了（P(allele-wise analysis) = 0.101）。总之，我们认为 HTR2A 可能在日本 MDD 患者 SSRIs 治疗反应的病理生理学中起重要作用。然而，使用大样本在其他独立研究中复制和确认这些发现将是很重要的。
