肿瘤坏死因子受体超家族rs767455多态性与散发性帕金森病相关性临床研究  

Influence of tumor necrosis factor receptor superfamily rs767455 polymorphisms on the age of onset and symptoms in the patients with sporadic Parkinson disease

作　　者：周涌涛[1] 刘佳[1] 张燕莉[1] 张新卿[1] 郭秀海[1] 陈彪[1] 贾建平[1] 

机构地区：[1]首都医科大学宣武医院神经内科,北京100053

出　　处：《中华脑科疾病与康复杂志（电子版）》2012年第4期5-9,共5页Chinese Journal of Brain Diseases and Rehabilitation（Electronic Edition）

基　　金：国家自然科学基金面上项目(30970926)

摘　　要：目的 探究肿瘤坏死因子受体超家族(TNFRSF) rs767455基因多态性在散发性帕金森病(SPD)患者中的分布及对发病年龄和临床特征的影响。方法 本研究应用TaqMan探针技术对2006年10月至2009年12月宣武医院及全国多中心药物试验的481例帕金森病(PD)患者(PD组)和557例正常对照个体(对照组)进行TNFRSF rs767455多态性检测,所有数据采用SPSS 11.5统计学软件进行处理,应用x2检验、非条件logistic回归模型分析、Kaplan-Meier和生命表方法分析基因多态性与SPD的相关性,及对SPD发病年龄的影响。另将PD组患者分为震颤组(298例)和非震颤组(183例),将两组的AA、AG、GG基因型及A、G等位基因的分布与对照组比较。结果 TNFRSFrs767455 AA、AG和GG基因型在PD组和对照组之间的分布差异无统计学意义(PD组:80.04％、19.13％、0.83％；对照组:79.00％、19.75％、1.25％;x2=0.53,P＞0.05)。也没有发现A和G等位基因的分布在PD组和对照组之间差异有统计学意义(x2=0.29,P＞0.05)。对性别进行调整后发现,TNFRSF rs767455 G等位基因对SPD发病仍无显著性影响(x2=0.01,P＞0.05)。AA、AG和GG基因型的发病年龄的中位数分别为61岁(95％ CI59 ～63岁)、61岁(95％ CI,57 ～65岁)和60岁(95％CI57 ～63岁),虽然携带AA基因型的发病年龄较AG、GG基因型提前,但差异无统计学意义(x2=0.54,P＞0.05),利用Cox-回归方法分析控制性别的影响仍没有发现GG影响发病年龄(x2=0.03,P＞0.05)。携带G和非G等位基因个体发病年龄的中位数分别为61岁(95％ CI59～63岁)与60岁(95％ CI56～64岁),利用生存分析进行研究发现携带A等位基因的个体并不能延迟SPD的发病年龄(x2 =0.36,P=0.55)。震颤组和非震颤组AA、AG、GG基因型及A、G等位基因的分布差异无统计学意义(x2 =1.94,0.15;P＞0.05)。结论 TNFRSF rs767455在SPD和对照组中分布无差异,且不影响SPD的发病年龄和临床表现。Objective To explore the distribution of tumor necrosis factor receptor superfamily( TNFRSF rs767455) polymorphism in patients with sporadic Parkinson disease( SPD),and whether the polymorphisms are associated with age and symptom. Methods The TNFRSF rs767455 polymorphisms of481 cases of Parkinson's disease( PD)( group PD) in Xuanwu hospital and the national drug testing center from October the 2006 to December the 2009 and 557 cases of controls( control group) were detected by TaqMan probe. The data was analyzed by SPSS 11. 5 software for windows. χ2test,multivariate logistic regression model and survival analysis( Kaplan-Meier analysis and life table) were used to tell the difference of genotype,the influence of TNFRSFrs767455 polymorphisms on the age of onset and symptoms in SPD. In addition,patients in PD group were divided into the tremor group and non-tremor group,AA,AG,GG genotypes and A / G allele distribution of the two groups were compared with control group. Results The distribution of TNFRSF rs767455genotypes and alleles had no difference between cases and controls( χ2=0. 53,P > 0. 05),A and G allele distribution between PD and control groups was not significant statistically.( χ2= 0. 29,P > 0. 05). We also found that there was no difference of TNFRSF rs767455 genotypes and alleles after stratified by age at onset and gender( χ2= 0. 01,P > 0. 05). The median age of GG genotype carriers was 60 years( 95% CI,57-63 years),patients with AA genotype were 61 years( 95% CI,59-63years),but there was no statistic difference between them( χ2= 0. 54,P > 0. 05). GG was not found to affect the age of onset by Cox-regression( χ2= 0. 03,P > 0. 05). The median age of individuals with G allele and non-G allele was 61 years( 95% CI,59-63 years) and 60 years( 95% CI,56-64 years). G allele did not delay the age at onset of SPD( log rank χ2= 0. 36,P = 0. 55). AA,AG,GG genotypes and A / G allele distribution of tremor group and non-tremor group has no statistical significance( χ2= 1. 94,0. 15,P > 0. 05). Conclusion

关 键 词：帕金森病 发病年龄 疾病特征 受体 肿瘤坏死因子 

分 类 号：R742.5[医药卫生—神经病学与精神病学]