Genetic determinants associated with response to clozapine in schizophrenia: an umbrella review.

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Psychiatric Genetics Pub Date : 2022-10-01 Epub Date: 2022-07-20 DOI:10.1097/YPG.0000000000000320

Marte Z van der Horst, Georgia Papadimitriou, Jurjen J Luykx

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引用次数: 0

Abstract

Objective: Clozapine response varies widely from person to person, which may be due to inter-individual genetic variability. This umbrella review aims to summarize the current evidence on associations between pharmacodynamic genes and response to clozapine treatment.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology, a systematic literature search was conducted in the PubMed and EMBASE databases from inception to November 2021 to identify systematic reviews and meta-analyses of studies that examined genetic determinants of clozapine response. The quality of the reviews was assessed with the AMSTAR-2 tool.

Results: From a total of 128 records, 10 studies representing nine systematic reviews and one meta-analysis met our inclusion criteria. The overall quality of the included studies was poor. All systematic reviews concluded that the results of primary studies were largely negative or conflicting. Most evidence was found for an association with clozapine response and rs6313 and rs6314 within HTR2A and rs1062613 within HTR3A in the serotonergic system.

Conclusions: Conclusive evidence for associations between genetic variants and clozapine response is still lacking. Hypothesis-generating genetic studies in large, well-characterized study populations are urgently needed to obtain more consistent and clinically informative results. Future studies may also include multi-omics approaches to identify novel genetic determinants associated with clozapine response.

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与精神分裂症患者对氯氮平反应相关的遗传决定因素：综述。

目的：对氯氮平的反应因人而异，这可能是由于个体间的基因差异造成的。本综述旨在总结药效学基因与氯氮平治疗反应之间关系的现有证据：方法：按照《系统综述和荟萃分析首选报告项目》的方法，在 PubMed 和 EMBASE 数据库中进行了系统文献检索（从开始到 2021 年 11 月），以确定研究氯氮平反应基因决定因素的系统综述和荟萃分析。采用AMSTAR-2工具对综述的质量进行评估：在总共 128 条记录中，有 10 项研究（代表 9 篇系统综述和 1 篇荟萃分析）符合我们的纳入标准。纳入研究的总体质量较差。所有系统综述的结论都是，主要研究的结果大多是负面的或相互矛盾的。大多数证据表明，氯氮平反应与血清素能系统中 HTR2A 的 rs6313 和 rs6314 以及 HTR3A 的 rs1062613 有关：目前仍缺乏基因变异与氯氮平反应相关的确凿证据。为了获得更一致、更有临床参考价值的结果，迫切需要在大规模、特征明确的研究人群中开展假设性遗传研究。未来的研究还可能包括多组学方法，以确定与氯氮平反应相关的新型基因决定因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychiatric Genetics 医学-神经科学

CiteScore

2.30

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： The journal aims to publish papers which bring together clinical observations, psychological and behavioural abnormalities and genetic data. All papers are fully refereed. Psychiatric Genetics is also a forum for reporting new approaches to genetic research in psychiatry and neurology utilizing novel techniques or methodologies. Psychiatric Genetics publishes original Research Reports dealing with inherited factors involved in psychiatric and neurological disorders. This encompasses gene localization and chromosome markers, changes in neuronal gene expression related to psychiatric disease, linkage genetics analyses, family, twin and adoption studies, and genetically based animal models of neuropsychiatric disease. The journal covers areas such as molecular neurobiology and molecular genetics relevant to mental illness. Reviews of the literature and Commentaries in areas of current interest will be considered for publication. Reviews and Commentaries in areas outside psychiatric genetics, but of interest and importance to Psychiatric Genetics, will also be considered. Psychiatric Genetics also publishes Book Reviews, Brief Reports and Conference Reports.