Levodopa-induced dyskinesia (LID) is a debilitating motor feature in a subset of patients with Parkinson’s disease (PD) after prolonged therapeutic administration of levodopa. Preliminary animal and human studies are suggestive of a key role of dopamine type 3 (D3) receptor polymorphism (Ser9Gly; rs6280) in LID. Its contribution to development of LID among Indian PD patients has remained relatively unexplored and merits further investigation. 200 well-characterised PD patients (100 without LID and 100 with LID) and 100 age-matched healthy controls were recruited from the outpatient department of Institute of Neurosciences Kolkata. MDS-UPDRS (Unified Parkinson’s Disease Rating Scale from International Movement Disorder Society) Part III and AIMS (abnormal involuntary movement scale) were performed for estimation of severity of motor features and LID respectively in the ON state of the disease. Participants were analysed for the presence of Ser9Gly single nucleotide variant (SNV) (rs6280) by polymerase chain reaction followed by restriction fragment length polymorphism techniques. The frequency of AA genotype (serine type) was more frequently present in PD patients with LID compared to PD patients without LID (50 % vs 28 %; P = 0.002; OR = 2.57, 95 % CI: 1.43 – 4.62). The abnormal involuntary movement scale score was significantly higher in PD patients with AA genotype compared to carriers of glycine allele (AG + GG) (4.08 ± 3.35; P = 0.002). We observed a significant association of serine type SNV (rs6280) in D3 receptor gene in a cohort of PD patients with LID from India. More severe motor severity was found in patients with glycine substitution of the same SNV. The current study emphasised the role of D3 receptor in the pathogenesis of LID.

中文翻译：

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多巴胺受体 D3 多态性与左旋多巴诱发的运动障碍的关联：对印度帕金森病患者的研究

左旋多巴诱发的运动障碍 (LID) 是帕金森病 (PD) 患者长期服用左旋多巴后出现的一种使人衰弱的运动特征。初步动物和人体研究表明 3 型多巴胺 (D3) 受体多态性（Ser9Gly；rs6280）在 LID 中发挥关键作用。它对印度 PD 患者 LID 发展的贡献相对尚未被探索，值得进一步研究。从加尔各答神经科学研究所门诊部招募了 200 名特征明确的 PD 患者（100 名无 LID，100 名有 LID）和 100 名年龄匹配的健康对照。MDS-UPDRS（国际运动障碍协会统一帕金森病评定量表）第三部分和 AIMS（异常不自主运动量表）分别用于估计疾病 ON 状态下运动特征和 LID 的严重程度。通过聚合酶链反应和限制性片段长度多态性技术，分析参与者是否存在 Ser9Gly 单核苷酸变异 (SNV) (rs6280)。与无 LID 的 PD 患者相比，患有 LID 的 PD 患者的 AA 基因型（丝氨酸型）频率更常见（50% vs 28%；P = 0.002；OR = 2.57，95% CI：1.43 – 4.62）。与甘氨酸等位基因（AG+GG）携带者相比，AA基因型PD患者异常不自主运动量表评分显着较高（4.08±3.35；P=0.002）。我们在一组来自印度的患有 LID 的 PD 患者中观察到 D3 受体基因中的丝氨酸型 SNV (rs6280) 存在显着关联。甘氨酸取代相同 SNV 的患者运动症状更严重。目前的研究强调了D3受体在LID发病机制中的作用。