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ABCB1基因多态性对抗抑郁药疗效的影响。

The Effect of ABCB1 Polymorphisms on the Efficacy of Antidepressants.

作者信息

Thorsen Sofie Voss, Bülow Cille, Dalhoff Kim, Sonne David Peick

机构信息

Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.

Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Basic Clin Pharmacol Toxicol. 2025 Oct;137(4):e70097. doi: 10.1111/bcpt.70097.

Abstract

This scoping review investigates the association between ABCB1 polymorphisms and antidepressant efficacy in humans. A systematic search identified 630 records, of which 58 met the inclusion criteria, resulting in 42 unique studies (five randomised controlled trials (RCTs), two randomised studies (non-RCTs), 30 prospective cohort studies, three case-control studies, one cross-sectional clinical study and one phase I clinical trial). These studies examined single nucleotide polymorphisms (SNPs) in or near the ABCB1 gene and their association with antidepressant treatment response. Of the 42 studies, 30 focused on rs1045642, the most extensively studied SNP. Among these, only 20% reported statistically significant associations. Beyond rs1045642, rs2032582 and rs1128503 were also frequently studied, but statistically significant associations were reported in only a minority of cases (28% and 13%, respectively), often with conflicting directions. Haplotype analyses involving all three SNPs (the TTT haplotype) showed mixed results. Results were variable across antidepressants, likely due to overlapping pharmacokinetic pathways. Methodological differences, including study design, sample sizes and definitions of remission, likely contribute to these inconsistencies. This review highlights the complexity of linking ABCB1 polymorphisms to antidepressant treatment response and suggests the need for standardised methodologies and larger, diverse populations in future studies. Haplotype analyses could provide deeper insights and enhance personalised treatment strategies.

摘要

本综述性研究调查了人类ABCB1基因多态性与抗抑郁药疗效之间的关联。系统检索共识别出630条记录,其中58条符合纳入标准,最终纳入42项独特的研究(5项随机对照试验(RCT)、2项随机研究(非RCT)、30项前瞻性队列研究、3项病例对照研究、1项横断面临床研究和1项I期临床试验)。这些研究检测了ABCB1基因内部或附近的单核苷酸多态性(SNP)及其与抗抑郁治疗反应的关联。在这42项研究中,30项聚焦于rs1045642,这是研究最广泛的SNP。其中,只有20%的研究报告了具有统计学意义的关联。除rs1045642外,rs2032582和rs1128503也经常被研究,但只有少数情况报告了具有统计学意义的关联(分别为28%和13%),且结果往往相互矛盾。涉及所有三个SNP的单倍型分析(TTT单倍型)结果不一。不同抗抑郁药的结果存在差异,可能是由于药代动力学途径重叠。包括研究设计、样本量和缓解定义在内的方法学差异,可能导致了这些不一致。本综述强调了将ABCB1基因多态性与抗抑郁治疗反应联系起来的复杂性,并表明未来研究需要标准化方法和更大规模、多样化的人群。单倍型分析可能会提供更深入的见解并优化个性化治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3021/12436669/2e0891268406/BCPT-137-0-g002.jpg

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