新疆地区帕金森病危险因素、症状学和ATP13A2基因多态性研究

发布时间：2018-03-30 20:31

  本文选题：帕金森病　切入点：危险因素　出处：《新疆医科大学》2015年博士论文

【摘要】：目的:①探讨新疆地区散发性帕金森病(Sporadic Parkinson’s disease,SPD)的危险因素以及维吾尔族和汉族SPD危险因素的差异性。②探讨新疆地区SPD患者临床症状学特点以及维吾尔族和汉族SPD患者临床症状学的差异性,并分析SPD患者认知功能、睡眠质量和情绪状态3组非运动症状的影响因素。③探讨新疆地区SPD患者ATP13A2基因Thr12Met和Ala1144Thr位点多态性以及维吾尔族和汉族SPD患者该基因位点多态性的差异性。方法:①新疆地区SPD危险因素分析:SPD患者(PD组)400例(其中汉族SPD210例,维族SPD190例);健康成人(对照组)400例(其中汉族202例,维族198例)。所有受试者均完成基本情况调查表、广泛性焦虑量表-7项(GAD-7)、病人健康问卷抑郁量表-9项(PHQ-9)、蒙特利尔认知评估量表(MoCA)和匹兹堡睡眠质量指数(PSQI)评分,均进行空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-c)、低密度脂蛋白(LDL-c)、尿酸(UA)、同型半胱氨酸(Hcy)及C-反应蛋白(CRP)水平检测。分析SPD危险因素,比较维吾尔族和汉族SPD危险因素的差异性。②新疆地区SPD临床症状学分析:受试者来源及方法同①,同时对SPD患者完成统一帕金森病评定量表(UPDRS)及Hoehn和Yahn(H-Y)分期,非运动症状评分量表,总结SPD患者临床症状学特点,比较维吾尔族和汉族SPD患者临床症状学的差异性,并分析认知功能、睡眠质量和情绪状态3组非运动症状的影响因素。③新疆地区SPD患者ATP13A2基因多态性分析:SPD患者(PD组)420例(其中汉族SPD220例,维族SPD200例)和健康成人(对照组)400例(其中汉族202例,维族198例)。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和基因测序方进行ATP13A2基因亚型Thr12Met位点多态性分析;采用聚合酶链反应(PCR)结合DNA直接测序法进行ATP13A2基因亚型Ala1144Thr多态性分析。比较两个民族SPD患者Thr12Met和Ala1144Thr位点的基因多态性的差异性。结果:①与对照组比较,PD组饮酒史和农药接触史较高(17.00%vs 34.25%和4.75%vs 12.25%,P0.05),吸烟史、饮茶史及饮咖啡史较少(43.25%vs 20.25%、63.00%vs 29.25%和11.50%vs 6.75%,P0.05);与汉族PD组相比,维吾尔族PD组吸烟史和饮酒史较少(13.25%vs 7.00%和22.25%vs 12.00%,P0.05),饮茶史较多(11.25%vs 18.00%,P0.05),饮咖啡史和农药接触史无差异(P0.05)。②与对照组比较,PD组TG、LDL-c和UA值较低(2.52±0.99 vs 1.97±0.88、2.78±0.65 vs 2.26±0.62和361.80±96.24 vs328.11±90.80,P0.05),Hcy值较高(8.90±4.49 vs 13.78±5.48,P0.05);与汉族PD组比较,维吾尔族PD组TG及LDL-c值较高(1.86±0.87 vs 2.07±0.89和2.00±0.62 vs 2.46±0.62,P0.05),TC、FBG、HDL-c、UA、Hcy和CRP值无差异(P0.05)。③首发症状、病程、起病年龄、UPDRS(I、II和III部分)及H-Y分级比较,维吾尔族和汉族PD组之间无差异(P0.05)。④SPD患者最常见的非运动症状是认知功能障碍、焦虑、抑郁、便秘和疲乏,与汉族PD组比较,维族PD组便秘和疲乏症状更多见(P0.05)。⑤新疆地区SPD的发病与饮酒史、农药接触史、Hcy值、PHQ-9和PSQI总分呈正相关(β分别为0.869、0.768、0.975、1.147和2.068),与吸烟史、饮茶史、饮咖啡史、TG、LDL-c和UA值呈负相关(β分别为-0.861、-2.613、-1.134、-2.155、-1.171和-2.914)。⑥与对照组比较,PD组MoCA、PSQI、PHQ-9和GAD-7异常率更高(5.75%vs 59.50%、6.25%vs 27.25%、7.50%vs45.50%和7%vs 58.25%,P0.05),其中MoCA评分与病程、体重和PHQ-9呈负相关(β分别为-0.833、-0.183和-0.330);PSQI评分与年龄、病程和PHQ-9呈正相关(β分别为0.718,0.156和0.148);PHQ-9总分与GAD-7呈正相关(β为0.631),与UA值呈负相关(β为-0.212)。MoCA、PSQI、PHQ-9和GAD-7评分及异常率比较,维吾尔族PD组和汉族PD组之间无差异(P0.05)。⑦新疆地区ATP13A2基因Thr12Met位点突变率为2/420(0.48%),Ala1144Thr位点突变率为1/420(0.24%);ATP13A2基因Thr12Met和Ala1144Thr位点多态性在PD组与对照组间、两民族间、男女性别间以及早发性PD(Early-onset Parkinson’s disease,EOPD)与晚发性PD(Late-onset Parkinson’s disease,LOPD)间比较无显著差异性(P0.05)。结论:①吸烟史、饮茶史及饮咖啡史是SPD的保护因素;饮酒史、农药接触史、睡眠障碍及抑郁是SPD发病的危险因素,低TG、低LDL-c、低UA和高Hcy增加SPD发病风险;两民族SPD在吸烟、饮酒、饮茶史、TG和LDL-c方面存在差异性;②SPD患者的认知功能与病程、体重指数和抑郁程度相关;睡眠障碍与年龄、病程和抑郁程度相关;抑郁与焦虑程度和UA值相关;两民族SPD患者在非运动症状便秘和疲乏方面存在差异性。③ATP13A2基因亚型Thr12Met和Ala1144Thr位点突变率在新疆地区SPD中极低;这两个位点的多态性在维吾尔族和汉族SPD中分布无显著差异性。
[Abstract]:Objective: To explore the Xinjiang area of sporadic Parkinson's disease (Sporadic Parkinson s disease, SPD) the difference of the risk factors and risk factors of Uygur and Han SPD. To explore the characteristics of Uygur and Han patients with SPD and clinical symptoms of the differences of the clinical symptoms of SPD patients in Xinjiang area, and analyze the cognitive function of patients with SPD, the factors affecting the quality of sleep and mood state of 3 groups of non motor symptoms. The differences between patients with SPD in Xinjiang region ATP13A2 gene Thr12Met and Ala1144Thr polymorphism in Uygur and Han patients with SPD and the gene polymorphism of Xinjiang area. Methods: to analyze the risk factors of SPD patients with SPD (PD group) 400 cases (including in SPD210 cases, SPD190 cases); Uygur healthy adults (control group) 400 cases (including 202 cases of Han, Uygur 198 cases). All subjects completed the basic situation questionnaire, extensive anxiety Table -7 (GAD-7), patient health questionnaire depression -9 (PHQ-9), Montreal cognitive assessment scale (MoCA) and Pittsburgh sleep quality index (PSQI) score were fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL-c), low density lipoprotein (LDL-c), uric acid (UA), homocysteine (Hcy) and C- reactive protein (CRP) level was detected. SPD analysis of risk factors, the differences between Uygur and Han SPD risk factors analysis in Xinjiang area. The clinical symptoms of SPD: the subjects and methods of the same source. At the same time to complete the unified Parkinson's disease rating scale of patients with SPD (UPDRS) and Hoehn (H-Y) and Yahn staging, non motor symptoms score, summarize the clinical symptoms of the patients with SPD characteristics, the difference between Uygur and Han patients with clinical symptoms of SPD, and analyze the cognitive function, sleep quality and emotional state of 3 groups exercise The analysis of the influence factors of symptoms. Patients with SPD in Xinjiang region ATP13A2 gene polymorphism in patients with SPD (PD group) 420 cases (including cases of Uygur Han SPD220, SPD200 cases) and healthy adults (control group) 400 cases (including 202 cases of Han, Uygur 198 cases). Using polymerase chain reaction restriction fragment length polymorphism of (PCR-RFLP) and gene sequencing analysis ATP13A2 gene of Thr12Met subtype polymorphism; polymerase chain reaction (PCR) combined with DNA direct sequencing analysis of ATP13A2 gene of Ala1144Thr subtype polymorphism. Differences between gene polymorphism comparison of two ethnic SPD patients Thr12Met and Ala1144Thr loci. Results: 1 and control compared to PD group, drinking history and the history of pesticide exposure is higher (17.00%vs 34.25% and 4.75%vs 12.25%, P0.05), smoking history, drinking history and drinking coffee history less (43.25%vs 20.25%, 63.00%vs 29.25% and 11.50%vs 6.75%, P0.05) and Han PD group; 鐩告瘮,缁村惥灏旀棌PD缁勫惛鐑熷彶鍜岄ギ閰掑彶杈冨皯(13.25%vs 7.00%鍜，

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