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目的:探讨多巴胺D_2受体(DRD_2)CA双核苷酸短串联重复序列(CA_n-STR)以及多巴胺D_3受体(DRD_3)Ser9Gly多态性与原发性帕金森病(PD)患者左旋多巴治疗个体差异的相关性。方法:选取88例原发性PD患者(PD组)以及90名健康对照者(对照组),抽取外周静脉血,分析DRD_2CA_n-STR和DRD_3Ser9Gly基因型。同时记录PD患者基本临床特征,包括起病年龄、病程、Hoehn和Yahr分期(H&Y分期)、左旋多巴剂量及等效剂量(LED),以及评估PD统一评定量表(UPDRS)、非运动症状评分量表(NMS)、汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)和简易精神状态检查(MMSE)量表等。比较PD患者不同基因型临床特征的差异,分析基因多态性与PD患者左旋多巴疗效的相关性。结果:2组间DRD_2CA_n-STR和DRD_3Ser9Gly基因型以及等位基因频率分布均无显著差异。不同DRD_2CA_n-STR基因型PD患者间临床特征无明显区别。而不同DRD_3Ser9Gly基因型PD患者间,Gly/Gly组患者UPDRS总分及第Ⅲ部分评分显著高于Ser/Gly以及Ser/Ser组(均P<0.01),各组LED和左旋多巴剂量无明显差异。多因素逐步回归模型结果表明DRD_3Ser9Gly基因型是UPDRS总分及第Ⅲ部分评分的独立危险因素(P<0.05)。结论 :DRD_3Ser9Gly多态性可影响患者对左旋多巴治疗的疗效,携带Gly/Gly基因型的患者可能需要更高剂量的左旋多巴才能取得较好的治疗效果。
Objective: To investigate the effect of levodopa treatment in patients with idiopathic Parkinson’s disease (PD) on polymorphisms of CA dinucleotide repeat sequence (CA_n-STR) and dopamine D_3 receptor (DRD_3) Ser9Gly at dopamine D_2 receptor (DRD_2) Correlation of individual differences. Methods: 88 primary PD patients (PD group) and 90 healthy controls (control group) were selected and peripheral venous blood was collected for the analysis of DRD2CA_n-STR and DRD3 Ser9Gly genotypes. At the same time, the basic clinical features of patients with PD were recorded, including age of onset, duration of disease, Hoehn and Yahr staging (H & Y staging), levodopa dosage and equivalent dose (LED), PD rating scale (UPDRS) (NMS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and Mini-Mental State Examination Scale (MMSE). The differences of clinical characteristics of different genotypes of PD patients were compared, and the correlation between gene polymorphisms and the efficacy of levodopa in PD patients was analyzed. Results: There was no significant difference in genotypes of DRD_2CA_n-STR and DRD_3Ser9Gly between two groups and allele frequency distribution. There was no significant difference in clinical features among patients with different DRD2CA_n-STR genotypes. However, in patients with DRD_3Ser9Gly genotype PD, the scores of UPDRS and III in Gly / Gly group were significantly higher than those in Ser / Gly and Ser / Ser groups (all P <0.01), and the dose of LED and levodopa in each group was not significantly difference. The stepwise multiple regression analysis showed that the DRD_3Ser9Gly genotype was an independent risk factor for the UPDRS score and III score (P <0.05). Conclusion: The DRD_3Ser9Gly polymorphism can affect the efficacy of levodopa treatment in patients with Gly / Gly genotype patients may require higher doses of levodopa in order to achieve better therapeutic effect.