Sun Qianqian, Yuan Fan, Yuan Ruixue, Ren Decheng, Zhu Yuhao, Bi Yan, Hu Jiaxin, Guo Zhenming, Xu Fei, Niu Weibo, Ma Gaini, Wu Xi, Yang Fengping, Wang Lu, Li Xingwang, Yu Tao, He Lin, He Guang
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Institute of Mental Health, Shanghai Jiao Tong University, Shanghai, China.
Medicine (Baltimore). 2019 May;98(19):e15456. doi: 10.1097/MD.0000000000015456.
Venlafaxine is one of commonly prescribed antidepressants for major depressive disorder (MDD). Accumulated evidence implicates the involvement of glutamatergic receptors in the pathophysiology of MDD and antidepressant treatment.By using 193 MDD patients who have been taking venlafaxine for 6 weeks, we investigated whether single nucleotide polymorphisms (SNPs) in glutamate ionotropic receptor kainate type subunit 4 (GRIK4), glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) and glutamate metabotropic receptor 7 (GRM7) were associated with treatment response. 14 SNPs were selected randomly depended on association studies. Efficacy of treatment was determined by 17-item of Hamilton Rating Scale. Allele and genotype frequencies were compared between responders and non-responders.After adjusting by the false discovery rate (FDR), rs6589847 and rs56275759 in GRIK4 and rs9870680 in GRM7 showed associating with venlafaxine treatment response at week 6. (FDR: P = .018, P = .042, and P = .040, respectively).Our results indicated that genetic variants in the GRIK4 and GRM7 may associate with the treatment response in MDD patients treated by venlafaxine.
文拉法辛是治疗重度抑郁症（MDD）常用的抗抑郁药之一。越来越多的证据表明，谷氨酸能受体参与了MDD的病理生理过程及抗抑郁治疗。我们选取了193例服用文拉法辛6周的MDD患者，研究谷氨酸离子型红藻氨酸受体4型亚基（GRIK4）、谷氨酸离子型AMPA受体1型亚基（GRIA1）和谷氨酸代谢型受体7（GRM7）中的单核苷酸多态性（SNP）是否与治疗反应相关。根据关联研究随机选择了14个SNP。治疗效果通过17项汉密尔顿评定量表来确定。比较了反应者和无反应者之间的等位基因和基因型频率。在通过错误发现率（FDR）校正后，GRIK4中的rs6589847和rs56275759以及GRM7中的rs9870680显示与第6周时文拉法辛的治疗反应相关（FDR：P分别为0.018、0.042和0.040）。我们的结果表明，GRIK4和GRM7中的基因变异可能与接受文拉法辛治疗的MDD患者的治疗反应相关。
