GRIK4 rs1954787 多态性与抗抑郁药治疗的抑郁症患者临床反应的关系:前瞻性队列和荟萃分析的结果

IF 9.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Kenneth Chappell, Romain Colle, Khalil El Asmar, Florence Gressier, Jérôme Bouligand, Séverine Trabado, Bruno Fève, Laurent Becquemont, Emmanuelle Corruble, Céline Verstuyft
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引用次数: 0

摘要

重度抑郁症(MDD)是导致全球残疾的主要原因。遗传因素会影响其主要治疗方案--抗抑郁药物(ATD)的效果。在一些研究中,GRIK4 rs1954787(T>C)基因多态性与1-3个月的ATD治疗后的反应有关,但在其他研究中则不然。我们的目的是在接受 ATD 治疗 6 个月的患者队列中分析其与临床结果的关系,并进行荟萃分析。我们获得了 METADAP 队列中 390 名患者在 ATD 治疗 1 个月(M1)、3 个月(M3)和 6 个月(M6)后的基线和临床数据。混合效应模型用于评估 GRIK4 rs1954787 多态性与汉密尔顿抑郁量表(HDRS)评分以及不同时期的反应率和缓解率之间的关系。利用先前的荟萃分析数据和METADAP对ATD治疗反应进行了荟萃分析。与M3时的C等位基因携带者(n = 200)相比,M3时的TT同系基因携带者(n = 66)具有更高的HDRS评分(系数 = 3.37,95% CI [1.30-5.54],Padj = 0.0046)和更低的缓解率(OR = 0.36,95% CI [0.16-0.76],Padj = 0.029)。在M6时,观察到TT等位基因携带者(n = 53)和C等位基因携带者(n = 152)在HDRS评分(系数 = 4.68,95% CI [2.17-7.18],Padj = 0.00091)和缓解率(OR = 0.26,95% CI [0.12-0.54],Padj = 0.0016)方面存在更大差异。当比较 C 等位基因与 T 等位基因(OR = 1.31,95% CI [1.06-1.62],P = 0.014)和 CC 基因型与 TT 基因型(OR = 1.63,95% CI [1.10-2.38],P = 0.019)时,反应的 Meta 分析具有显著性。总之,我们的研究结果支持 GRIK4 rs1954787(T>C)多态性与 ATD 治疗后的临床改善有关。这种关联应在其他纵向研究中进一步评估。它在谷氨酸能系统中的位置可能有助于理解 ATD 的作用机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Association of the GRIK4 rs1954787 polymorphism with clinical response in antidepressant-treated depressed patients: results from a prospective cohort and meta-analysis

Association of the GRIK4 rs1954787 polymorphism with clinical response in antidepressant-treated depressed patients: results from a prospective cohort and meta-analysis

Major Depressive Disorder (MDD) is the leading cause of disability worldwide. Genetic factors influence the effect of its main treatment option, antidepressant drugs (ATD). The GRIK4 rs1954787(T>C) genetic polymorphism was associated with response following 1–3 months of ATD treatment in some studies, but not others. We aimed to analyze its association with clinical outcomes in a cohort of 6-month ATD-treated patients and meta-analysis. Clinical data were obtained at baseline and after 1 (M1), 3 (M3), and 6 (M6) months of ATD treatment in 390 patients of the METADAP cohort. Mixed-effects models were used to assess the association of the GRIK4 rs1954787 polymorphism with the Hamilton Depression Rating Scale (HDRS) score and response and remission rates across time. Meta-analyses of ATD treatment response were performed with previously meta-analyzed data and METADAP. Compared to C allele carriers at M3 (n = 200), TT homozygotes at M3 (n = 66) had higher HDRS scores (coef = 3.37, 95% CI [1.30–5.54], Padj = 0.0046) and lower remission rates (OR = 0.36, 95% CI [0.16–0.76], Padj = 0.029). At M6, greater differences between TT homozygotes (n = 53) and C allele carriers (n = 152) were observed for HDRS scores (coef = 4.68, 95% CI [2.17–7.18], Padj = 0.00091) and remission rates (OR = 0.26, 95% CI [0.12–0.54], Padj = 0.0016). Meta-analyses of response were significant when comparing C vs T alleles (OR = 1.31, 95% CI [1.06–1.62], P = 0.014) and CC vs TT genotypes (OR = 1.63, 95% CI [1.10–2.38], P = 0.019). Altogether, our results support an association of the GRIK4 rs1954787(T>C) polymorphism with clinical improvement following ATD treatment. This association should be further assessed in other longitudinal studies. Its position within the glutamatergic system may help in understanding the mechanism of ATD action.

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来源期刊
Molecular Psychiatry
Molecular Psychiatry 医学-精神病学
CiteScore
20.50
自引率
4.50%
发文量
459
审稿时长
4-8 weeks
期刊介绍: Molecular Psychiatry focuses on publishing research that aims to uncover the biological mechanisms behind psychiatric disorders and their treatment. The journal emphasizes studies that bridge pre-clinical and clinical research, covering cellular, molecular, integrative, clinical, imaging, and psychopharmacology levels.
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