ATP13A2基因亚型Ala746Thr和Thr12met突变与新疆维吾尔族早发型和家族型帕金森病临床的相关研究

Parkinson's disease (Parkinson's disease PD) is a degenerative diseases of the central nervous system, which is commonly occured in aged people and mostly showed disease-associated dementia in advanced phase. Morbidity of PD not only seriously affected the quality of the patients' life but also increased the social and economic burden to the country and their family. Epidemiological survey showed that PD prevalence is vary among different ethnics and differtent familial region and 10% of PD patients had family history. Studies have shown that ATPl3A2 is susceptibility genes which might be lead to PD prevalence.ATPl3A2 gene had relationship with autosomal recessive hereditary PD and ATPl3A2 gene mutation showed the typical earlier clinical features. Some studies suggested that the its subtype gene Ala746Thr and Thr12Met mutation showed relationship with early-onset and familial PD while there was some different research report. Until now few reports described the correlation between the ATP13A2 genetic mutation and early-onset and familial PD in Xinjiang Uygur population. The present study used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) approaches to investigate the ATP13A2 gene polymorphism and mutability in early-onset and familial PD in Xinjiang Uygur population. This research will provide the basic information for understanding PD pathogenesis with ethnic discrepancy; furthermore it will provide the theoretical basis for diagnosis,treatment and prevention of PD in its early stage for Xinjiang Uygur population.

帕金森病（parkinson's disease,PD）是一种中老年人常见的中枢神经系统变性疾病，晚期多伴有痴呆，严重影响患者的生活质量，给国家和家庭带来沉重的社会和经济负担。流调显示PD发病具有种族差异性和家族性（约占PD的15％）。有研究表明ATP13A2基因是PD的易感致病基因，与常染色体隐性遗传性PD相关，其基因突变具有典型早发临床特征。其中Ala746Thr和Thr12Met突变类型与不同种族早发型和家族型PD相关，但也有不同的研究报道。目前尚未见有关于新疆地区维吾尔族早发型和家族型PD 与ATP13A2基因相关性研究报道。本研究拟采用PCR- RFLP等技术，探讨ATP13A2基因多态性和突变性与新疆地区维吾尔族人群早发型和家族型PD发病的关系以及与临床症状及预后的相关性；为PD的发病机制提供民族差异遗传学基础研究；并为新疆地区维吾尔族人群PD的早期诊治和预防提供理论依据。

帕金森病（parkinson's disease,PD）是一种中老年人常见的中枢神经系统变性疾病。本课题收集来自新疆各地的PD患者1587例，构建了PD临床资料库。再此基础上提取患者DNA样本，构建了PD的DNA样本库。同时采用分子生物学基因检测技术，分析新疆地区维吾尔族和汉族早发型及家族型PD患者ATP13A2基因Ala746、Thr12Met分布及突变特点，同时扩大样本含量进一步研究了新的突变位点Ala1144Thr、rs151117874、C.1815C>T（rs2076603））、（Arg294Gln）、rs56367069（Arg294.Gln）、rs56379718（Gly49Ser）、rs151117874（Thr12Met）、rs147277743（Ala746Thr）和rs2076603）与PD的关系，并取得了相应的成果。Ala1144Thr位点不同基因表型（野生型CC与杂合变异CT型）及Thr12Met位点不同基因表型（野生型GG与杂合变异型AG）PD患者临床资料分析结果显示Ala1144Thr位点发生CT基因型杂合突变见于EOPD（Early-onset parkinsonism，EOPD）患者中，在LOPD(Late-onset Parkinson’ s disease，LOPD)患者中未发现任何突变。Thr12Met位点发生AG型杂合变异均见于EOPD患者中，在LOPD患者中未发现任何突变。该实验结果为PD的发病机制提供不同民族差异遗传学基础研究；并为新疆地区PD的早期诊治和预防提供理论依据。共发表文章13篇。