Levodopa (LD) is the gold standard for the treatment of Parkinson’s disease (PD). Genetic polymorphisms in the SLC6A3 gene (Solute carrier family 6 member 3/DAT-Dopamine Transporter gene) are shown to have a functional impact on levodopa therapeutic response, motor complications of PD and adverse events. Hence the present study was carried out to investigate the association of SLC6A3 polymorphisms with the pharmacokinetics of levodopa and clinical response. A total of 150 PD patients were recruited in the study. Plasma levodopa was analysed by HPLC at 0, 1, 2, 3 and 4 h post levodopa administration and AUC was calculated. Genotyping of SLC6A3 40 bp VNTR and SLC6A3 rs393795 (G>T) polymorphisms was done by the PCR-RFLP method. The result shows that AUC of levodopa was significantly higher in patients carrying homozygous10/10 genotype (P =0008) compared to 9/9 genotype of SLC6A3 40 bp VNTR polymorphism. A similar difference was also observed in early-onset Parkinson’s disease (EOPD) and late-onset Parkinson’s disease (LOPD) groups. SLC6A310/10 genotype was found to be significantly associated with disease severity (P =0.05) compared with the 9/10 genotype in the EOPD group, however, there was no significant association with dyskinesia. To conclude, patients carrying SLC6A3 40VNTR 10/10 genotype were found to have higher levodopa exposure, disease severity and prone to further neurodegeneration.

中文翻译：

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SLC6A3基因多态性与帕金森病患者左旋多巴的药代动力学和临床结局的关系

左旋多巴（LD）是治疗帕金森氏病（PD）的金标准。SLC6A3基因（Solute载体家族6成员3 / DAT-多巴胺转运蛋白基因）中的遗传多态性显示对左旋多巴的治疗反应，PD的运动并发症和不良事件具有功能性影响。因此，本研究旨在研究SLC6A3多态性与左旋多巴的药代动力学和临床反应之间的关系。该研究共招募了150名PD患者。左旋多巴给药后0、1、2、3和4小时通过HPLC分析左旋多巴血浆，并计算AUC。SLC6A3 40 bp VNTR和SLC6A3 rs393795（G> T）多态性的基因分型通过PCR-RFLP方法完成。结果表明，与SLC6A3 40 bp VNTR多态性的9/9基因型相比，携带纯合子10/10基因型（P = 0008）的患者左旋多巴的AUC显着更高。在早发性帕金森氏病（EOPD）和晚发性帕金森氏病（LOPD）组中也观察到类似的差异。与EOPD组的9/10基因型相比，发现SLC6A310 / 10基因型与疾病严重程度显着相关（P = 0.05），但是，与运动障碍没有显着相关性。总而言之，发现携带SLC6A3 40VNTR 10/10基因型的患者具有更高的左旋多巴暴露，疾病严重性和容易发生进一步的神经变性。在早发性帕金森氏病（EOPD）和晚发性帕金森氏病（LOPD）组中也观察到类似的差异。与EOPD组的9/10基因型相比，发现SLC6A310 / 10基因型与疾病严重程度显着相关（P = 0.05），但是与运动障碍没有显着相关性。总而言之，发现携带SLC6A3 40VNTR 10/10基因型的患者具有更高的左旋多巴暴露，疾病严重性和容易发生进一步的神经变性。在早发性帕金森氏病（EOPD）和晚发性帕金森氏病（LOPD）组中也观察到类似的差异。与EOPD组的9/10基因型相比，发现SLC6A310 / 10基因型与疾病严重程度显着相关（P = 0.05），但是与运动障碍没有显着相关性。总而言之，发现携带SLC6A3 40VNTR 10/10基因型的患者具有更高的左旋多巴暴露，疾病严重性和容易发生进一步的神经变性。