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散发性帕金森病患者的药物遗传学特征与幻视的发生。

Pharmacogenetic Profile and the Occurrence of Visual Hallucinations in Patients With Sporadic Parkinson's Disease.

机构信息

Graduate Program in Applied Cellular and Molecular Biology, University of Pernambuco (UPE), Recife, PE, Brazil.

Graduate Program in Applied Biology for Health, Federal University of Pernambuco (UFPE), Recife, PE, Brazil.

出版信息

J Clin Pharmacol. 2019 Jul;59(7):1006-1013. doi: 10.1002/jcph.1394. Epub 2019 Feb 22.

Abstract

Visual hallucinations are significant nonmotor symptoms in the course of treatment of Parkinson's disease. Previous studies have shown that the interindividual variability and pharmacogenetic profile of Parkinson's disease patients seem to influence the occurrence of visual hallucinations. In our study, we investigated a possible relationship of sequence variants in DRD1, DRD2, DRD3, DAT1, and COMT genes with the presence of visual hallucinations in Parkinson's disease patients. A total of 224 Brazilian patients from the Pro-Parkinson service at the Clinical Hospital of the University of Pernambuco, diagnosed with sporadic Parkinson's disease, were enrolled. Parkinson's disease patients were divided into 2 groups based on the presence or absence of visual hallucinations. The sequence variants for DRD1, DRD2, DRD3, DAT1, and COMT were determined through the polymerase chain reaction-restriction fragment length polymorphism technique. Multiple Poisson regression analyses showed that individuals carrying the DRD3 Ser/Ser and Ser/Gly genotypes presented increased prevalence ratios of visual hallucinations (9.7-fold and 4.4-fold, respectively; P < .001). Regarding DAT1 rs28363170, there was a 9.82-fold increase in the prevalence ratio in patients with the 10/11 genotype, 8.78-fold for the 10/8 genotype, and 2.44-fold for the 9/8 genotypes (P < .001, for all). In addition, visual hallucinations were also associated with use of transdermal patches with rotigotine (PR, 3.7; 95%CI, 1.2-10.9; P = .017) and rasagiline (PR, 2.8; 95%CI, 1.3-6.0; P = .006). Our results suggest that the genetic variants DRD3 and DAT1, along with other therapeutic confounders, may influence the prevalence ratio of visual hallucinations.

摘要

视觉幻觉是帕金森病治疗过程中的重要非运动症状。先前的研究表明,帕金森病患者的个体间变异性和药物遗传学特征似乎会影响视觉幻觉的发生。在我们的研究中,我们研究了 DRD1、DRD2、DRD3、DAT1 和 COMT 基因中的序列变异与帕金森病患者视觉幻觉存在的可能关系。我们共纳入了来自巴西伯南布哥大学临床医院 Pro-Parkinson 服务的 224 名患者,这些患者被诊断为散发性帕金森病。根据是否存在视觉幻觉,将帕金森病患者分为 2 组。通过聚合酶链反应-限制性片段长度多态性技术确定了 DRD1、DRD2、DRD3、DAT1 和 COMT 的序列变异。多因素泊松回归分析显示,携带 DRD3 Ser/Ser 和 Ser/Gly 基因型的个体视觉幻觉的患病率比值增加(分别为 9.7 倍和 4.4 倍;P<.001)。关于 DAT1 rs28363170,10/11 基因型、10/8 基因型和 9/8 基因型患者的患病率比值分别增加了 9.82 倍、8.78 倍和 2.44 倍(P<.001,均)。此外,视觉幻觉还与使用罗替高汀透皮贴片(PR,3.7;95%CI,1.2-10.9;P=0.017)和雷沙吉兰(PR,2.8;95%CI,1.3-6.0;P=0.006)有关。我们的结果表明,DRD3 和 DAT1 遗传变异以及其他治疗混杂因素可能会影响视觉幻觉的患病率比值。

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