α-突触核蛋白基因多态性与帕金森病非运动症状的关联

Association study of α-synuclein gene polymorphism and non motor symptoms in Parkinson＆#39;s disease

目的 探讨α-突触核蛋白（SNCA）中2个单核苷酸多态性（SNP）位点rs894278和rs11931074与帕金森病非运动症状之间的关系.方法 选择2012年至2014年上海交通大学医学院附属瑞金医院桐庐分院第一人民医院和上海交通大学医学院附属瑞金医院神经内科门诊、住院诊治的120例帕金森病患者与100名健康对照,采用统一帕金森病评定量表（UPDRS）的第三部分（UPDRS-Ⅲ）以及Hoehn＆Yahr分期、简易精神状态检查量表（MMSE）、汉密尔顿抑郁评定量表17（HAMD-17）、快速眼动期睡眠行为障碍（RBD）筛查问卷（RBDSQ）、罗马Ⅲ便秘标准（ROME-Ⅲ）进行运动症状与非运动症状的评定;利用聚合酶链反应结合连接酶检测反应方法扩增汉族帕金森病人群中SNCA 2个SNP位点rs894278和rs11931074,分析各基因型及其和非运动症状之间的关系.结果 对照组2个SNP位点各基因型之间年龄、性别、非运动症状评分差异无统计学意义,而帕金森病组2个SNP位点各基因型之间年龄、性别、UPDRS-Ⅲ评分以及Hoehn＆Yahr分期差异也无统计学意义.SNP位点各基因型之间,MMSE评分、RBDSQ评分、便秘、HAMD-17评分差异均无统计学意义.进一步分析显示,对于SNP位点rs894278,GG型中可能的临床RBD所占比例比GT型、TT型更大（GG52.2％,12/23;GT 18.2％,10/55;TT 21.4％,9/42;χ^2=9.254,P=0.002;χ^2=6.424,P=0.005）.利用二分类Logistic回归分析在校正年龄、性别影响因素后,发现rs894278 GG基因型明显增加帕金森病患者RBD的风险（OR =5.367,95％ CI=1.607 ～ 17.925,P=0.006）.rs11931074的等位基因与基因型在伴/不伴RBD两组帕金森病患者之间的分布差异无统计学意义.结论 SNCA基因多态性位点rs894278与RBD相关联,rs11931074与RBD无关.

Objective To investigate the association between the single nucleotide polymorphisms （SNPs） rs894278 and rs11931074 of α-synuclein （SNCA） and non motor symptoms in Parkinson＇ s disease （PD）.Methods One hundred and twenty PD patients and 100 healthy controls enrolled from Tonglu Hospital Affiliated to Ruijin Hospital and Ruijin Hospital,Shanghai Jiaotong University School of Medicine from 2012 to 2014 were recruited and the motor subscale of the Unified Parkinson＇ s Disease Rating Scale Ⅲ （UPDRS-Ⅲ） was used to evaluate motor function.The Mini-Mental State Examination （MMSE）,17-item Hamilton Rating Scale （HAMD-17）,the Rapid Eye Movement Behavior Disorder Screening Questionnaire （RBDSQ） and the ROME-Ⅲ criteria for chronic constipation were used to evaluate non motor symptoms.SNCA SNPs （rs894278,rs11931074） were genotyped by direct sequencing.Results There was no statistically significant difference in age,sex,non motor symptoms scores among the three genotypes of the two SNPs in control group.There was no statistically significant difference in age,sex,UPDRS-Ⅲ scores and Hoehn-Yahr stage among the three genotypes of the two SNPs in PD group.The results demonstrated that there was no association between the two SNPs and RBDSQ scores,HAMD-17 scores,MMSE scores and constipation in PD patients.However,additional analysis showed that patients with GG rs894278 had a greater proportion of clinical probable RBD than those with GT and TT types （GG 52.2%,12/23;GT 18.2%,10/55;TT 21.4%,9/42;χ^2 =9.254,P=0.002;χ^2=6.424,P=0.005）.In Logistic regression analyses adjusting for age and sex,we observed that rs894278 GG genotype could increase the risk of RBD in PD patients （OR =5.367,95% CI =1.607-17.925,P =0.006）.There was no association of RBD with allelic and genotypic distributions of SNCA rs11931074.Conclusion The results indicate that the rs894278 polymorphism correlates with RBD,while rs11931074 does not.