SLC6A3 和 DRD2 多态性对散发性帕金森病患者左旋多巴治疗的影响。
The influence of SLC6A3 and DRD2 polymorphisms on levodopa-therapy in patients with sporadic Parkinson's disease.
机构信息
Postgraduate Program of Applied Cellular and Molecular Biology, University of Pernambuco (UPE), Recife, PE, Brazil.
Postgraduate Program of Applied Biology for Health, Federal University of Pernambuco (UFPE), Recife, PE, Brazil.
出版信息
J Pharm Pharmacol. 2019 Feb;71(2):206-212. doi: 10.1111/jphp.13031. Epub 2018 Oct 23.
OBJECTIVES
The aim of this study was to evaluate a possible relationship between DRD2/ANKK1 (rs1800497) and SLC6A3/DAT1 (rs28363170) gene polymorphisms with the response to levodopa (L-DOPA)-therapy in patients with Parkinson's disease (PD).
METHODS
One hundred and ninety-five patients with idiopathic PD were investigated. Patients were genotyped for rs1800497 and rs28363170 polymorphisms using PCR-RFLP. Logistic regression was performed to assess the association of polymorphisms with the occurrence of the chronic complications of L-DOPA therapy.
KEY FINDINGS
Our results showed association between the occurrence of dyskinesia with an increased greater disease severity (P = 0.007), higher L-DOPA dose (P = 0.007) and use of dopamine agonist (P = 0.020). Moreover, there were significant protective effects for age (P = 0.004) and male subjects (P = 0.006).
CONCLUSIONS
Clinical and demographic characteristics of Brazilian PD patients and differences in DRD2 and DAT1 genes may to determine individual variations in the therapeutic response to L-DOPA in the Brazilian PD patients.
目的
本研究旨在评估 DRD2/ANKK1（rs1800497）和 SLC6A3/DAT1（rs28363170）基因多态性与帕金森病（PD）患者对左旋多巴（L-DOPA）治疗反应之间的可能关系。
方法
研究纳入了 195 名特发性 PD 患者。采用 PCR-RFLP 法对 rs1800497 和 rs28363170 多态性进行基因分型。采用逻辑回归评估多态性与 L-DOPA 治疗慢性并发症发生的相关性。
主要发现
我们的结果显示，运动障碍的发生与疾病严重程度增加（P=0.007）、L-DOPA 剂量更高（P=0.007）和使用多巴胺激动剂（P=0.020）有关。此外，年龄（P=0.004）和男性（P=0.006）具有显著的保护作用。
结论
巴西 PD 患者的临床和人口统计学特征以及 DRD2 和 DAT1 基因的差异可能决定了巴西 PD 患者对 L-DOPA 治疗反应的个体差异。
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