Pharmacogenetics of obsessive-compulsive disorder: Investigations of intragenic and regulatory region genetic variations

IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-04-02 Epub Date: 2025-03-05 DOI:10.1016/j.pnpbp.2025.111315
Gwyneth Zai , Clement C. Zai , Vanessa F. Gonçalves , Karen Wigg , Christine Lochner , Dan J. Stein , Carol A. Mathews , James L. Kennedy , Margaret A. Richter
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Abstract

Few pharmacogenetic studies on the use of genetic variations to predict antidepressant response in obsessive-compulsive disorder (OCD) have been published. This study expanded on the limited literature on single nucleotide polymorphisms (SNPs) across previously identified putative susceptibility genes for OCD, by incorporating known functional regulatory elements for all genes of interest. We investigated 17 SNPs in 12 genes implicated in OCD risk in 206 European ancestry OCD patients with selective serotonin reuptake inhibitor (SSRI) antidepressant response data, examining functional polymorphisms in remote regulatory regions. No association was observed between any regulatory region markers tested and drug response. We observed nominally significant associations between SNPs within the serotonin 1B receptor (5HT1B; SNP rs1778258), SLIT and NTRK-like family member 5 (SLITRK5; SNP rs10450811), and fas apoptotic inhibitory molecule 2 (FAIM2; SNP rs706795), with response to any SSRI, which did not survive multiple comparisons. This study supports a potential role for a number of OCD-associated risk genes in response to antidepressant treatment, warranting further investigation.
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强迫症的药物遗传学:基因内和调控区遗传变异的研究。
利用遗传变异预测强迫症(OCD)抗抑郁反应的药物遗传学研究很少发表。本研究通过纳入所有感兴趣基因的已知功能调控元件,扩展了先前确定的强迫症推定易感基因中单核苷酸多态性(snp)的有限文献。我们研究了206名欧洲血统强迫症患者选择性5 -羟色胺再摄取抑制剂(SSRI)抗抑郁反应数据中12个与强迫症风险相关基因中的17个snp,检查了远程调控区域的功能多态性。没有观察到任何调节区域标记物与药物反应之间的关联。我们观察到5 -羟色胺1B受体(5HT1B;SNP rs1778258), SLIT和ntrk样家族成员5 (SLITRK5;SNP rs10450811)和fas凋亡抑制分子2 (FAIM2;SNP rs706795),对任何SSRI均有反应,但多次比较均无效。这项研究支持了一些与强迫症相关的风险基因在抗抑郁治疗反应中的潜在作用,值得进一步研究。
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来源期刊
CiteScore
12.00
自引率
1.80%
发文量
153
审稿时长
56 days
期刊介绍: Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject. Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.
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