SNCA 与帕金森病的关联：哈佛神经发现中心生物标志物研究的复制。
Association of SNCA with Parkinson: replication in the Harvard NeuroDiscovery Center Biomarker Study.
机构信息
Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Cambridge, Massachusetts, USA.
出版信息
Mov Disord. 2011 Oct;26(12):2283-6. doi: 10.1002/mds.23934. Epub 2011 Sep 23.
Abstract
BACKGROUND
Mutations in the α-synuclein gene (SNCA) cause autosomal dominant forms of Parkinson's disease, but the substantial risk conferred by this locus to the common sporadic disease has only recently emerged from genome-wide association studies.
METHODS
We genotyped a prioritized noncoding variant in SNCA intron 4 in 344 patients with Parkinson's disease and 275 controls from the longitudinal Harvard NeuroDiscovery Center Biomarker Study.
RESULTS
The common minor allele of rs2736990 was associated with elevated disease susceptibility (odds ratio, 1.40; P = .0032).
CONCLUSIONS
This result increases confidence in the notion that in many clinically well-characterized patients, genetic variation in SNCA contributes to "sporadic" disease.
摘要
背景
α-突触核蛋白基因 (SNCA) 的突变导致常染色体显性形式的帕金森病，但该基因座对常见散发性疾病的巨大风险仅最近才从全基因组关联研究中显现出来。
方法
我们对来自纵向哈佛神经发现中心生物标志物研究的 344 名帕金森病患者和 275 名对照者的 SNCA 内含子 4 中的优先非编码变异进行了基因分型。
结果
常见的 rs2736990 次要等位基因与疾病易感性升高相关（比值比，1.40；P =.0032）。
结论
这一结果增加了这样一种观念的可信度，即在许多临床特征良好的患者中，SNCA 的遗传变异导致了“散发性”疾病。
相似文献
1
Association of SNCA with Parkinson: replication in the Harvard NeuroDiscovery Center Biomarker Study.SNCA 与帕金森病的关联：哈佛神经发现中心生物标志物研究的复制。
Mov Disord. 2011 Oct;26(12):2283-6. doi: 10.1002/mds.23934. Epub 2011 Sep 23.
2
Association of polymorphism in rs2736990 of the α-synuclein gene with Parkinson's disease in a Chinese population.α-突触核蛋白基因 rs2736990 多态性与中国人群帕金森病的关联。
Neurol India. 2013 Jul-Aug;61(4):360-4. doi: 10.4103/0028-3886.117595.
3
Parkinson's disease correlates with promoter methylation in the α-synuclein gene.帕金森病与α-突触核蛋白基因的启动子甲基化相关。
Mov Disord. 2015 Apr;30(4):577-80. doi: 10.1002/mds.26073. Epub 2014 Dec 27.
4
A comprehensive analysis of SNCA-related genetic risk in sporadic parkinson disease.对散发型帕金森病中 SNCA 相关遗传风险的综合分析。
Ann Neurol. 2018 Jul;84(1):117-129. doi: 10.1002/ana.25274. Epub 2018 Aug 26.
5
An updated analysis with 45,078 subjects confirms the association between SNCA rs11931074 and Parkinson's disease.一项纳入 45078 例受试者的更新分析证实了 SNCA rs11931074 与帕金森病之间的关联。
Neurol Sci. 2018 Dec;39(12):2061-2069. doi: 10.1007/s10072-018-3538-4. Epub 2018 Aug 17.
6
SNCA rs356182 variant increases risk of sporadic Parkinson's disease in ethnic Chinese.SNCA基因rs356182变异体增加了中国汉族人群患散发性帕金森病的风险。
J Neurol Sci. 2016 Sep 15;368:231-4. doi: 10.1016/j.jns.2016.07.032. Epub 2016 Jul 14.
7
SNCA polymorphisms, smoking, and sporadic Parkinson's disease in Japanese.SNCA 多态性、吸烟与日本散发性帕金森病。
Parkinsonism Relat Disord. 2012 Jun;18(5):557-61. doi: 10.1016/j.parkreldis.2012.02.016. Epub 2012 Mar 17.
8
Risk variants of the α-synuclein locus and REM sleep behavior disorder in Parkinson's disease: a genetic association study.帕金森病中α-突触核蛋白基因座的风险变异与快速眼动睡眠行为障碍：一项基因关联研究。
BMC Neurol. 2018 Feb 21;18(1):20. doi: 10.1186/s12883-018-1023-6.
9
Replication of MAPT and SNCA, but not PARK16-18, as susceptibility genes for Parkinson's disease.MAPT 和 SNCA 的复制，而不是 PARK16-18，是帕金森病的易感基因。
Mov Disord. 2011 Apr;26(5):819-23. doi: 10.1002/mds.23642. Epub 2011 Mar 21.
10
Hypomethylation of SNCA in blood of patients with sporadic Parkinson's disease.散发性帕金森病患者血液中α-突触核蛋白的低甲基化
J Neurol Sci. 2014 Feb 15;337(1-2):123-8. doi: 10.1016/j.jns.2013.11.033. Epub 2013 Dec 1.
引用本文的文献
1
Advancing Parkinson's Disease Research in Canada: The Canadian Open Parkinson Network (C-OPN) Cohort.推进加拿大帕金森病研究：加拿大开放帕金森网络（C-OPN）队列。
J Parkinsons Dis. 2024;14(7):1481-1494. doi: 10.3233/JPD-240213.
2
Proteome profiling of cerebrospinal fluid reveals biomarker candidates for Parkinson's disease.脑脊液蛋白质组谱分析揭示帕金森病的生物标志物候选物。
Cell Rep Med. 2022 Jun 21;3(6):100661. doi: 10.1016/j.xcrm.2022.100661.
3
A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson's disease.帕金森病中常见SNCA变异与临床异质性之间关联的系统评价。
NPJ Parkinsons Dis. 2021 Jul 1;7(1):54. doi: 10.1038/s41531-021-00196-5.
4
Epigenetics in Lewy Body Diseases: Impact on Gene Expression, Utility as a Biomarker, and Possibilities for Therapy.路易体病中的表观遗传学：对基因表达的影响、作为生物标志物的效用，以及治疗的可能性。
Int J Mol Sci. 2020 Jul 2;21(13):4718. doi: 10.3390/ijms21134718.
5
β-Glucocerebrosidase activity in -linked Parkinson disease: The type of mutation matters.- 连接型帕金森病中β-葡糖脑苷脂酶活性：突变类型很重要。
Neurology. 2020 Aug 11;95(6):e685-e696. doi: 10.1212/WNL.0000000000009989. Epub 2020 Jun 15.
6
Associations of Lower Caffeine Intake and Plasma Urate Levels with Idiopathic Parkinson's Disease in the Harvard Biomarkers Study.低咖啡因摄入量和血浆尿酸水平与哈佛生物标志物研究中的特发性帕金森病的关联。
J Parkinsons Dis. 2020;10(2):505-510. doi: 10.3233/JPD-191882.
7
The Personalized Parkinson Project: examining disease progression through broad biomarkers in early Parkinson's disease.个性化帕金森项目：通过早期帕金森病中的广泛生物标志物来研究疾病进展。
BMC Neurol. 2019 Jul 17;19(1):160. doi: 10.1186/s12883-019-1394-3.
8
Potential two-step proteomic signature for Parkinson's disease: Pilot analysis in the Harvard Biomarkers Study.帕金森病潜在的两步蛋白质组学特征：哈佛生物标志物研究中的初步分析。
Alzheimers Dement (Amst). 2019 May 2;11:374-382. doi: 10.1016/j.dadm.2019.03.001. eCollection 2019 Dec.
9
Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's.具体而言，神经性戈谢病突变会加速帕金森病患者的认知衰退。
Ann Neurol. 2016 Nov;80(5):674-685. doi: 10.1002/ana.24781.
10
Current Challenges Towards the Development of a Blood Test for Parkinson's Disease.当前开发帕金森病血液检测方法所面临的挑战。
Diagnostics (Basel). 2014 Oct 22;4(4):153-64. doi: 10.3390/diagnostics4040153.
本文引用的文献
1
PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.PGC-1α，帕金森病早期干预的潜在治疗靶点。
Sci Transl Med. 2010 Oct 6;2(52):52ra73. doi: 10.1126/scitranslmed.3001059.
2
Genome-wide association study reveals genetic risk underlying Parkinson's disease.全基因组关联研究揭示帕金森病的遗传风险。
Nat Genet. 2009 Dec;41(12):1308-12. doi: 10.1038/ng.487. Epub 2009 Nov 15.
3
GATA transcription factors directly regulate the Parkinson's disease-linked gene alpha-synuclein.GATA转录因子直接调控与帕金森病相关的基因α-突触核蛋白。
Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10907-12. doi: 10.1073/pnas.0802437105. Epub 2008 Jul 31.
4
Multiple regions of alpha-synuclein are associated with Parkinson's disease.α-突触核蛋白的多个区域与帕金森病相关。
Ann Neurol. 2005 Apr;57(4):535-41. doi: 10.1002/ana.20438.
5
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.
6
The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service.专科运动障碍诊疗机构中帕金森综合征的诊断准确性
Brain. 2002 Apr;125(Pt 4):861-70. doi: 10.1093/brain/awf080.
7
Effect of allelic variation at the NACP-Rep1 repeat upstream of the alpha-synuclein gene (SNCA) on transcription in a cell culture luciferase reporter system.α-突触核蛋白基因（SNCA）上游NACP-Rep1重复序列的等位基因变异对细胞培养荧光素酶报告系统中转录的影响。
Hum Mol Genet. 2001 Dec 15;10(26):3101-9. doi: 10.1093/hmg/10.26.3101.
Zotero 插件