Association analysis of SIGMAR1 with major depressive disorder and SSRI response
Association analysis of SIGMAR1 with major depressive disorder and SSRI response
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DOI：
10.1016/j.neuropharm.2010.02.013
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发表时间：
2010-06-01
影响因子：
4.7
通讯作者：
Iwata, Nakao
中科院分区：
文献类型：
--
作者：
Kishi, Taro;Yoshimura, Reiji;Iwata, Nakao
背景资料：一些研究表明，sigma 1非阿片样物质细胞内受体1（sigma 1受体）可能参与重度抑郁症（MDD）的病理生理。Sigma 1受体也是选择性5-羟色胺再摄取抑制剂（SSRIs）的主要药理学治疗靶点之一。为了评价sigma 1受体基因（SIGMAR 1）与MDD和SSRIs治疗MDD反应的相关性，我们对日本样本进行了病例对照研究（466例MDD患者，516例对照组和208例接受氟伏沙明或舍曲林治疗的MDD患者）。我们将临床反应定义为汉密尔顿抑郁量表（SIGH-D）结构化访谈指南基线下降50%以上在8周内，并且在8周时临床缓解为SIGH-D评分小于7。因此，我们选择SIGMAR 1中的rs 1800866基因型进行以下关联分析。结果：在Logistic回归分析中，我们发现rs 1800866基因型与表型（MDD或对照）相关。然而，我们没有发现rs 1800866和SSRI治疗反应之间的关联在日本MDD。此外，SSRI缓解与rs 1800866无关。此外，我们没有检测到一个新的多态性SIGMAR 1当我们进行了突变搜索使用MDD治疗SSRIs samples.Conclusion：我们的研究结果表明，在SIGMAR 1的rs 1800866可能发挥作用，在日本人口的MDD的病理生理。此外，SIGMAR 1在日本MDD患者对SSRI的治疗反应中不起作用。然而，由于我们的样本量较小，因此需要使用另一人群和更大样本进行重复研究才能得出结论性结果。(C)皇冠版权所有2010出版的爱思唯尔有限公司保留所有权利。
Background: Several investigations have suggested the possible involvement of sigma1 non-opioid intracellular receptor 1 (sigma1 receptor) in the pathophysiology of major depressive disorder (MDD). Sigma1 receptors are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors (SSRIs). To evaluate the association of sigma1 receptor gene (SIGMAR1) and MDD and SSRIs therapeutic response in MDD, we conducted a case control study of Japanese samples (466 MDD patients, 516 controls and 208 MDD patients treated by fluvoxamine or sertraline).Method: We defined a clinical response as a decrease of more than 50% in baseline the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Therefore, we selected rs1800866 in SIGMAR1 for the following association analysis.Results: In the logistic regression analysis, we detected an association of the phenotypes (MDD or controls) with rs1800866 genotype. However, we did not detect an association between rs1800866 and SSRI therapeutic response in Japanese MDD. In addition, remission with SSRI was not associated with rs1800866. Also, we did not detect a novel polymorphism in SIGMAR1 when we performed a mutation search using MDD treated by SSRIs samples.Conclusion: Our results suggest that rs1800866 in SIGMAR1 may play a role in the pathophysiology of MDD in the Japanese population. Also, SIGMAR1 does not play a role in the therapeutic response to SSRI in Japanese MDD patients. However, because our sample was small, a replication study using another population and larger sample will be required for conclusive results. (C) Crown Copyright 2010 Published by Elsevier Ltd. All rights reserved.