HTR2A is Associated with SSRI Response in Major Depressive Disorder in a Japanese Cohort
HTR2A is Associated with SSRI Response in Major Depressive Disorder in a Japanese Cohort
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DOI：
10.1007/s12017-009-8105-y
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发表时间：
2010-09-01
影响因子：
3.5
通讯作者：
Iwata, Nakao
中科院分区：
文献类型：
--
作者：
Kishi, Taro;Yoshimura, Reiji;Iwata, Nakao
最近的一些研究报告，5-羟色胺2A受体基因（HTR 2A）与选择性5-羟色胺再摄取抑制剂（SSRIs）在抑郁症。在日本MDD患者中也有两项报告了HTR 2A与SSRI反应的相关性分析，但结果相当不一致，两项研究都存在样本量小的问题。因此，我们进行了一项复制关联研究，使用的样本大于两项原始日本研究（265例MDD患者）的样本，发现HTR 2A中的4个SNP，即2个功能性SNP（-A1438 G：rs6311和T102 C：rs6313）和2个SNP（rs7997012和rs 1928040）与SSRI的治疗反应相关。在单体型分析中，HTR 2A与日本MDD患者的SSRI治疗反应相关（P（所有标记物）= 0.0136），在MDD中检测到HTR 2A中的rs 1928040与SSRI反应之间的显著相关性（P（等位基因分析）= 0.0252）。然而，这种显著性在Bonferroni校正后消失（P（等位基因分析）= 0.101）。总之，我们认为HTR 2A可能在日本MDD患者对SSRIs治疗反应的病理生理学中发挥重要作用。然而，重要的是在其他使用大样本的独立研究中复制和确认这些发现。
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.