多巴胺D_2受体CA_n-STR和D_3受体Ser9Gly基因多态性与左旋多巴治疗相关性研究  

Association of dopamine receptor D type 2 CA_n-STR and dopamine receptor D type 3 Ser9Gly polymorphisms with response to L-dopa treatment

作　　者：徐绍卿 刘久江[1,2] 杨晓东[1,2] 钱逸维 肖勤[1,2] 

机构地区：[1]上海交通大学医学院附属瑞金医院神经内科 [2]上海交通大学医学院神经病学研究所,上海200025

出　　处：《内科理论与实践》2016年第3期170-175,共6页Journal of Internal Medicine Concepts & Practice

基　　金：国家自然科学基金项目(项目编号:81071023);上海市科学技术委员会科研计划项目(项目编号:14ZR1425700)

摘　　要：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 association between dopamine receptor D type 2 （DRD2） dinucleotide short tandem repeat （CAn-STR） as well as dopamine receptor D type 3 （DRD3） Ser9Gly polymorphisms and response to L-dopa treatment in Parkinson＇s disease （PD）. Methods The genotypes of DRD2 CAs-STR and DRD3 Ser9Gly were detectedin 88 idiopathic PD patients and 90 normal controls. Clinical features such as age of onset, duration of the disease, Hoehn and Yahr （H ＆ Y） stage, L-dopa equivalent dose（LED）, and doses of L-dopa were collected from all the PD patients, unified Parkinson＇s disease rating scale（UPDRS）, neuroleptic malignant syndrome（NMS）, Hamilton anxiety scale （HAMA）, Hamilton depression rating scale （HAMD）, and mini mental state examination（MMSE） were also scored. The differences of clinical features between different genotypes, as well as the association between the genotypes and response to L-dopa were analyzed. Results There were no significant differences in DRDECA-STR and DRD3 Ser9Gly genotypes and in allele frequencies between PD patients and controls. There were no differences in the clinical features between DRD2CAn-STR genotypes. Among three different DRD3 Ser9Gly genotypes, the UPDRS scores in total and part 111 in the Gly/Gly group were significantly higher than in the Ser/Gly and Ser/Ser group （P〈0.01）. The LED and doses of L-dopa were not obviously different among three groups. Multiple stepwise linear regression model showed that DRD3 Ser9Gly genotype was an independent risk factor for UPDRS scores in total and part m （P〈0.05）. Conclusions DRD3 Ser9Gly polymorphism may have an effect on response to L-dopa therapy and PD patients carrying Gly/Gly genotype might require higher doses of L-dopa for effective treatment.

关 键 词：帕金森病 多巴胺D2受体CA双核苷酸短串联重复序列 多巴胺D3受体Ser9Gly 左旋多巴 

分 类 号：R742.5[医药卫生—神经病学与精神病学]