α-synuclein基因启动子变异性和帕金森病的协同分析  

Collaborative analysis of α-synuclein gene promoter variability and Parkinson disease

作　　者：Maraganore D. M. De Andrade M. Elbaz A. 郭俊(译) 

机构地区：[1]Department of Neurology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, United States [2]不详

出　　处：《世界核心医学期刊文摘（神经病学分册）》2006年第12期1-2,共2页Digest of the World Core Medical Journals:Clinical Neurology

摘　　要：Context:Identification and replication of susceptibility genes for Parkinson disease at the population level have been hampered by small studies with potential biases.α-Synuclein(SNCA)has been one of the most promising susceptibility genes,but large-scale studies have been lacking.Objective:To determine whether allele-length variability in the dinucleotide repeat sequence(REP1)of the SNCA gene promoter is associated with Parkinson disease susceptibility,whether SNCA promoter haplotypes areassociated with Parkinson disease,and whether REP1 variability modifies age at onset.Design,Setting,and Participants:We performed a collaborative analysis of individual-level data on SNCA REP1 and flanking markers in patients with Parkinson disease and controls.Study site recruitment,data collection,and analyses were performed between April 5,2004,and December 31,2005.Eighteen participating sites of a global genetics consortium provided clinical data.Genotyping was performed for SNCA REP1,-770,and-116 markers at individual sites;however,each site also provided 20 DNA samples for regenotyping centrally.Main Outcome Measures:Measures included estimations of Hardy-Weinberg equilibrium in controls;a test of heterogeneity;analyses for association of single variants or haplotypes;and survival analyses for age at onset.Results:Of the 18 sites,11 met stringent criteria for concordance with Hardy-Weinberg equilibrium and low genotyping error rate.These 11 sites provided complete data for 2692 cases and 2652 controls.There was no heterogeneity across studies(P >.60).The SNCA REP1 alleles differed in frequency for cases and controls(P >.001).Genotypes defined by the 263 base-pair allele were associated with Parkinson disease(odds ratio,1.43;95%confidence interval,1.22-1.69;P <.001 for trend).Multilocus haplotypes differed in frequency for cases and controls(global score statistic,P <.001).Two-loci haplotypes were associated with Parkinson disease only when they included REP1 as one of the loci.However,genotypes defined by REP1 alleles didContext： Identification and replication of susceptibility genes for Parkinson disease at the population level have been hampered by small studies with potential biases. α-Synuclein （SNCA） has been one of the most promising susceptibility genes, but large-scale studies have been lacking. Objective： To determine whether allele-length variability in the dinucleotide repeat sequence （REP1） of the SNCA gene promoter is associated with Parkinson disease susceptibility, whether SNCA promoter haplotypes areassociated with Parkinson disease, and whether REP1 variability modifies age at onset. Design, Setting, and Participants： We performed a collaborative analysis of individual-level data on SNCA REP1 and flanking markers in patients with Parkinson disease and controls. Study site recruitment, data collection, and analyses were performed between April 5, 2004, and December 31, 2005. Eighteen participating sites of a global genetics consortium provided clinical data. Genotyping was performed for SNCA REP1, -770, and -116 markers at individual sites; however, each site also provided 20 DNA samples for regenotyping centrally. Main Outcome Measures： Measures included estimations of Hardy-Weinberg equilibrium in controls; a test of heterogeneity; analyses for association of single variants or haplotypes; and survival analyses for age at onset. Results： Of the 18 sites, 11 met stringent criteria for concordance with Hardy-Weinberg equilibrium and low genotyping error rate. These 11 sites provided complete data for 2692 cases and 2652 controls. There was no heterogeneity across studies （P 〉 . 60）. The SNCA REP1 alleles differed in frequency for cases and controls （P〉 .001）

关 键 词：基因启动子区 Α-SYNUCLEIN 帕金森病 变异性 协同 基因型分析 单体型频率 等位基因频率 

分 类 号：R562.25[医药卫生—呼吸系统]