A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms

IF 2.9 3区医学 Q2 GENETICS & HEREDITY

Pharmacogenomics Journal Pub Date : 2009-06-09 DOI:10.1038/tpj.2009.26

P Gassó, S Mas, M Bernardo, S Álvarez, E Parellada, A Lafuente

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引用次数: 50

Abstract

We present a pharmacogenetic study of acute antipsychotic (AP)-induced extrapyramidal symptoms (EPS) using an extensive linkage disequilibrium mapping approach in seven-candidate genes with a well-established link to dopamine (DRD2, DRD3, ACE, COMT, DAT, MAO-A, MAO-B). From a cohort of 321 psychiatric inpatients, 81 cases presenting with EPS (Simpson–Angus >3) and 189 controls presenting without EPS (Simpson–Angus ⩽3) took part. Eighty-four-tag single nucleotide polymorphisms (SNPs) in candidate genes were genotyped. After extensive data cleaning, 70 SNPs were analyzed for association of single markers and haplotypes. AP dosage, AP-DRD2 blockade potency and age were identified as susceptibility factors for AP-induced EPS. One SNP of the DRD3 gene, rs167771, achieved significant association with EPS risk after Bonferroni correction (nominal P-value 1.3 × 10−4) in the patients treated with risperidone (132 patients). AP-induced EPS remains a serious public health problem. Our finding of a common SNP (rs167771) in the DRD3 gene provides a strong new candidate gene for risperidone-induced EPS.

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DRD3基因的常见变异与利培酮诱发的锥体外系症状有关

我们对急性抗精神病药（AP）诱发的锥体外系症状（EPS）进行了一项药物遗传学研究，该研究采用了一种广泛的连锁不平衡图谱方法，研究了与多巴胺（DRD2、DRD3、ACE、COMT、DAT、MAO-A、MAO-B）有明确联系的七个候选基因。在 321 名精神病住院患者中，有 81 例 EPS 患者（辛普森-安格斯指数为 3）和 189 例无 EPS 患者（辛普森-安格斯指数为 3）。对候选基因中的 84 个标签单核苷酸多态性（SNP）进行了基因分型。经过大量数据清理后，对 70 个 SNPs 进行了单标记和单倍型关联分析。AP剂量、AP-DRD2阻断效力和年龄被确定为AP诱发EPS的易感因素。在接受利培酮治疗的患者（132 人）中，DRD3 基因的一个 SNP rs167771 经 Bonferroni 校正后（标称 P 值为 1.3 × 10-4）与 EPS 风险有显著关联。AP 引起的 EPS 仍是一个严重的公共卫生问题。我们在 DRD3 基因中发现的一个常见 SNP（rs167771）为利培酮诱发 EPS 提供了一个强有力的新候选基因。

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来源期刊

Pharmacogenomics Journal 医学-药学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.