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首页> 外文期刊>Journal of clinical psychopharmacology >The association study of polymorphisms in DAT, DRD2, and COMT genes and acute extrapyramidal adverse effects in male schizophrenic patients treated with haloperidol
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The association study of polymorphisms in DAT, DRD2, and COMT genes and acute extrapyramidal adverse effects in male schizophrenic patients treated with haloperidol

机译：氟哌啶醇治疗男性精神分裂症患者DAT，DRD2和COMT基因多态性与急性锥体外系不良反应的相关性研究

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Extrapyramidal symptoms (EPSs) are common adverse effects of antipsychotics. The development of acute EPSs could depend on the activity of dopaminergic system and its gene variants. The aim of this study was to determine the association between dopaminergic type 2 receptor (DRD2) dopamine transporter (SLC6A3) and catechol-O-methyltransferase (COMT) gene polymorphisms and acute EPSs in 240 male schizophrenic patients treated with haloperidol (15-mg/d) over a period of 2 weeks. Acute EPSs were assessed with Simpson-Angus Scale. Three dopaminergic gene polymorphisms, the DRD2 Taq1A, the SLC6A3 VNTR, and the COMT Val158Met, were determined.Extrapyramidal symptoms occurred in 116 (48.3%) of patients. Statistically significant associations were found for SLC6A3 VNTR and COMT Val158Met polymorphisms and EPS susceptibility. Patients with SLC6A3 9/10 genotype had almost twice the odds to develop EPSs compared with those with all other SLC6A3 genotypes (odds ratio, 1.9; 95% confidence interval, 1.13-3.30), and patients with COMT Val/Met genotype had 1.7 times greater odds to develop EPSs than those with all other COMT genotypes (odds ratio, 1.7; 95% confidence interval, 1.01-2.88). There was no statistically significant association between genotype and allele frequencies of DRD2, SLC6A3, or COMT polymorphisms and the development of particular EPSs.In conclusion, the results of the present study showed for the first time the association between acute haloperidol-induced EPSs and SLC6A3 VNTR and COMT Val158Met polymorphisms. Although the precise biological mechanisms underlying these findings are not yet understood, the results suggest that the dopaminergic gene variations could predict the vulnerability to the development of the acute EPSs in haloperidol-treated schizophrenic patients.
机译：锥体外系症状（EPS）是抗精神病药的常见不良反应。急性EPS的发展可能取决于多巴胺能系统及其基因变异的活性。这项研究的目的是确定240例氟哌啶醇（15-mg / ml）治疗的男性精神分裂症患者的多巴胺能2型受体（DRD2）多巴胺转运蛋白（SLC6A3）和儿茶酚-O-甲基转移酶（COMT）基因多态性与急性EPS之间的相关性d）在2周内。用辛普森-安格斯量表评估急性EPS。确定了三种多巴胺能基因多态性，即DRD2 Taq1A，SLC6A3 VNTR和COMT Val158Met.116名患者（48.3％）发生了锥体外系症状。发现SLC6A3 VNTR和COMT Val158Met多态性与EPS易感性具有统计学意义的关联。 SLC6A3 9/10基因型患者发生EPS的几率几乎是所有其他SLC6A3基因型患者的几率（赔率，1.9; 95％置信区间，1.13-3.30），而COMT Val / Met基因型患者的EPS的1.7倍。与所有其他COMT基因型的EPS相比，发生EPS的可能性更大（赔率为1.7; 95％置信区间为1.01-2.88）。 DRD2，SLC6A3或COMT多态性的基因型和等位基因频率与特定EPS的发生之间无统计学意义的相关性。总之，本研究的结果首次显示了氟哌啶醇诱导的EPS与SLC6A3的相关性。 VNTR和COMT Val158Met多态性。尽管尚不清楚这些发现背后的确切生物学机制，但结果表明，多巴胺能基因变异可以预测氟哌啶醇治疗的精神分裂症患者急性EPS发展的脆弱性。

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