Li Heng-Fen, Yu Xue, Yang Kun, He Cha-Ye, Kou Shao-Jie, Cao Su-Xia, Xie Guang-Rong
Department of Psychiatry, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, P.R. China.
Genet Test Mol Biomarkers. 2012 Jul;16(7):667-71. doi: 10.1089/gtmb.2011.0232. Epub 2012 Apr 5.
To explore the possible relationship between six single nucleotide polymorphisms (SNPs) (rs6311 and rs6305 of 5-HT2A, rs5443 of Gβ3, rs2230739 of ACDY9, rs1549870 of PDE1A and rs255163 of CREB1, which are all related with 5-HT2A the signal transduction pathway) and the response efficacy to selective serotonin reuptake inhibitor (SSRI) treatments in major depressive disorder (MDD) Chinese.
This study included 194 depressed patients to investigate the influence of 6 polymorphisms in 5-HT2A signal transduction-related genes on the efficacy of SSRIs assessed over 1 year. The efficacies of SSRIs on 194 MDD patients were evaluated in an 8-week open-trial study. Over 1 year, a follow-up study was completed for 174 of them to observe the long-term efficacy of SSRIs. The optimal-scaling regression analysis was used for testing the relationship between the different genotypes of five SNPs and the efficacy in MDD.
It showed that the patients with rs5443TT and rs2230739GG have a relatively good efficacy in response to short-term SSRIs. We also found that good efficacy appeared in depressed patients with rs2230739GG in response to long-term SSRIs.
It suggested that different genotypes of rs5443 and rs2230739 might influence the signal transduction pathways of second message and affect therapeutic efficacy.
探讨六个单核苷酸多态性(SNP)(5-HT2A的rs6311和rs6305、Gβ3的rs5443、ACDY9的rs2230739、PDE1A的rs1549870以及CREB1的rs255163,均与5-HT2A信号转导通路相关)与中国重度抑郁症(MDD)患者对选择性5-羟色胺再摄取抑制剂(SSRI)治疗反应疗效之间的可能关系。
本研究纳入194名抑郁症患者,调查5-HT2A信号转导相关基因中的6个多态性对1年内评估的SSRI疗效的影响。在一项为期8周的开放试验研究中评估了SSRI对194名MDD患者的疗效。1年多来,对其中174名患者完成了一项随访研究,以观察SSRI的长期疗效。采用最优尺度回归分析来检验五个SNP的不同基因型与MDD疗效之间的关系。
结果显示,rs5443TT和rs2230739GG的患者对短期SSRI的反应疗效相对较好。我们还发现,rs2230739GG的抑郁症患者对长期SSRI有良好疗效。
提示rs5443和rs2230739的不同基因型可能影响第二信使信号转导通路并影响治疗效果。