突触核蛋白α（SNCA）变体与多系统萎缩风险增加相关。
SNCA variants are associated with increased risk for multiple system atrophy.
作者信息
Scholz Sonja W, Houlden Henry, Schulte Claudia, Sharma Manu, Li Abi, Berg Daniela, Melchers Anna, Paudel Reema, Gibbs J Raphael, Simon-Sanchez Javier, Paisan-Ruiz Coro, Bras Jose, Ding Jinhui, Chen Honglei, Traynor Bryan J, Arepalli Sampath, Zonozi Ryan R, Revesz Tamas, Holton Janice, Wood Nick, Lees Andrew, Oertel Wolfgang, Wüllner Ullrich, Goldwurm Stefano, Pellecchia Maria Teresa, Illig Thomas, Riess Olaf, Fernandez Hubert H, Rodriguez Ramon L, Okun Michael S, Poewe Werner, Wenning Gregor K, Hardy John A, Singleton Andrew B, Del Sorbo Francesca, Schneider Susanne, Bhatia Kailash P, Gasser Thomas
机构信息
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA.
出版信息
Ann Neurol. 2009 May;65(5):610-4. doi: 10.1002/ana.21685.
Abstract
To test whether the synucleinopathies Parkinson's disease and multiple system atrophy (MSA) share a common genetic etiology, we performed a candidate single nucleotide polymorphism (SNP) association study of the 384 most associated SNPs in a genome-wide association study of Parkinson's disease in 413 MSA cases and 3,974 control subjects. The 10 most significant SNPs were then replicated in additional 108 MSA cases and 537 controls. SNPs at the SNCA locus were significantly associated with risk for increased risk for the development of MSA (combined p = 5.5 x 10(-12); odds ratio 6.2) [corrected].
摘要
为了检验突触核蛋白病帕金森病和多系统萎缩（MSA）是否具有共同的遗传病因，我们在413例MSA患者和3974例对照受试者中，对帕金森病全基因组关联研究中384个最相关的单核苷酸多态性（SNP）进行了候选SNP关联研究。随后，在另外108例MSA患者和537例对照中对10个最显著的SNP进行了重复验证。SNCA基因座处的SNP与MSA发生风险增加显著相关（合并p = 5.5 x 10(-12)；优势比6.2）[校正后] 。
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本文引用的文献
1
PLINK: a tool set for whole-genome association and population-based linkage analyses.PLINK：一个用于全基因组关联分析和基于群体的连锁分析的工具集。
Am J Hum Genet. 2007 Sep;81(3):559-75. doi: 10.1086/519795. Epub 2007 Jul 25.
2
Multiplex families with multiple system atrophy.患有多系统萎缩的多重家庭。
Arch Neurol. 2007 Apr;64(4):545-51. doi: 10.1001/archneur.64.4.545.
3
Quantitative PCR-based screening of alpha-synuclein multiplication in multiple system atrophy.基于定量PCR的多系统萎缩中α-突触核蛋白倍增的筛查
Parkinsonism Relat Disord. 2007 Aug;13(6):340-2. doi: 10.1016/j.parkreldis.2006.12.005. Epub 2007 Feb 8.
4
Gene expression changes in postmortem tissue from the rostral pons of multiple system atrophy patients.多系统萎缩患者脑桥上部尸检组织中的基因表达变化。
Mov Disord. 2007 Apr 30;22(6):766-77. doi: 10.1002/mds.21259.
5
Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication.由于α-突触核蛋白（SNCA）基因重复和三倍体导致的一个大型瑞典家系中的表型变异。
Neurology. 2007 Mar 20;68(12):916-22. doi: 10.1212/01.wnl.0000254458.17630.c5. Epub 2007 Jan 24.
6
Transcriptional changes in multiple system atrophy and Parkinson's disease putamen.多系统萎缩和帕金森病壳核的转录变化。
Exp Neurol. 2006 Jun;199(2):465-78. doi: 10.1016/j.expneurol.2006.01.008. Epub 2006 Apr 19.
7
The alpha-synuclein gene in multiple system atrophy.多系统萎缩中的α-突触核蛋白基因
J Neurol Neurosurg Psychiatry. 2006 Apr;77(4):464-7. doi: 10.1136/jnnp.2005.073528.
8
Probable multiple system atrophy in a German family.德国家庭中可能的多系统萎缩症
J Neurol Neurosurg Psychiatry. 2004 Jun;75(6):924-5. doi: 10.1136/jnnp.2003.025155.
9
The law of mass action applied to neurodegenerative disease: a hypothesis concerning the etiology and pathogenesis of complex diseases.质量作用定律应用于神经退行性疾病：关于复杂疾病病因和发病机制的一种假说。
Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R123-6. doi: 10.1093/hmg/ddh093. Epub 2004 Feb 19.
10
alpha-Synuclein locus triplication causes Parkinson's disease.α-突触核蛋白基因座三倍体导致帕金森病。
Science. 2003 Oct 31;302(5646):841. doi: 10.1126/science.1090278.
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