دورية أكاديمية
أعرض في EDS

Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy.

التفاصيل البيبلوغرافية
العنوان: Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy.
المؤلفون: Al-Chalabi A; MRC Centre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, and NIHR Biomedical Research Centre, London, United Kingdom. ammar@iop.kcl.ac.uk, Dürr A, Wood NW, Parkinson MH, Camuzat A, Hulot JS, Morrison KE, Renton A, Sussmuth SD, Landwehrmeyer BG, Ludolph A, Agid Y, Brice A, Leigh PN, Bensimon G
مؤلفون مشاركون: NNIPPS Genetic Study Group
المصدر: PloS one [PLoS One] 2009 Sep 22; Vol. 4 (9), pp. e7114. Date of Electronic Publication: 2009 Sep 22.
نوع المنشور: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Genetic Variation* , Polymorphism, Single Nucleotide*, Multiple System Atrophy/*genetics , alpha-Synuclein/*genetics, Aged ; Case-Control Studies ; Female ; Genotype ; Humans ; Male ; Microsatellite Repeats ; Middle Aged ; Multiple System Atrophy/pathology ; Quality Control ; alpha-Synuclein/physiology
مستخلص: Background: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and autonomic dysfunction. Pathogenic mechanisms remain obscure but the neuropathological hallmark is the presence of alpha-synuclein-immunoreactive glial cytoplasmic inclusions. Genetic variants of the alpha-synuclein gene, SNCA, are thus strong candidates for genetic association with MSA. One follow-up to a genome-wide association of Parkinson's disease has identified association of a SNP in SNCA with MSA.
Methodology/findings: We evaluated 32 SNPs in the SNCA gene in a European population of 239 cases and 617 controls recruited as part of the Neuroprotection and Natural History in Parkinson Plus Syndromes (NNIPPS) study. We used 161 independently collected samples for replication. Two SNCA SNPs showed association with MSA: rs3822086 (P = 0.0044), and rs3775444 (P = 0.012), although only the first survived correction for multiple testing. In the MSA-C subgroup the association strengthened despite more than halving the number of cases: rs3822086 P = 0.0024, OR 2.153, (95% CI 1.3-3.6); rs3775444 P = 0.0017, OR 4.386 (95% CI 1.6-11.7). A 7-SNP haplotype incorporating three SNPs either side of rs3822086 strengthened the association with MSA-C further (best haplotype, P = 8.7 x 10(-4)). The association with rs3822086 was replicated in the independent samples (P = 0.035).
Conclusions/significance: We report a genetic association between MSA and alpha-synuclein which has replicated in independent samples. The strongest association is with the cerebellar subtype of MSA.
Trial Registration: ClinicalTrials.gov NCT00211224.
References: Rev Neurol (Paris). 1992;148(4):274-80. (PMID: 1332174)
Neurosci Lett. 1997 Jan 17;221(2-3):161-4. (PMID: 9121689)
Mov Disord. 1995 May;10(3):277-8. (PMID: 7651442)
Neurology. 2008 Aug 26;71(9):670-6. (PMID: 18725592)
Ann Neurol. 2009 May;65(5):610-4. (PMID: 19475667)
Neurology. 2000 Dec 26;55(12):1918-20. (PMID: 11134398)
Mov Disord. 2005 Aug;20(8):1031-3. (PMID: 15838855)
Neurosci Lett. 2005 Feb 28;375(2):112-6. (PMID: 15670652)
Hum Genet. 2003 Oct;113(5):426-31. (PMID: 12923682)
Am J Med Genet A. 2003 Jul 15;120A(2):234-6. (PMID: 12833405)
Brain. 2009 Jan;132(Pt 1):156-71. (PMID: 19029129)
Am J Hum Genet. 2007 Sep;81(3):559-75. (PMID: 17701901)
Mov Disord. 2002 Jul;17(4):808-11. (PMID: 12210881)
Brain Res Mol Brain Res. 2005 Aug 18;138(2):178-81. (PMID: 15907346)
Nat Genet. 2007 Jul;39(7):906-13. (PMID: 17572673)
J Neurol Sci. 2006 Jan 15;240(1-2):107-10. (PMID: 16307759)
J Neurol Neurosurg Psychiatry. 2006 Apr;77(4):464-7. (PMID: 16543523)
J Neurol Sci. 2005 Jan 15;228(1):11-3. (PMID: 15607204)
Ann Neurol. 2004 Oct;56(4):591-5. (PMID: 15455394)
J Neurol Neurosurg Psychiatry. 2004 Jun;75(6):924-5. (PMID: 15146018)
Mov Disord. 2003 Nov;18(11):1385-6. (PMID: 14639688)
Brain. 1964 Dec;87:719-28. (PMID: 14236014)
J Neuropathol Exp Neurol. 1990 Sep;49(5):521-30. (PMID: 1703225)
Neurosci Lett. 1999 Jul 30;270(2):110-2. (PMID: 10462110)
Arch Neurol. 2007 Apr;64(4):545-51. (PMID: 17420317)
Mov Disord. 2008 Jun 15;23(8):1161-7. (PMID: 18442140)
J Neurol Sci. 2006 Nov 15;249(2):115-21. (PMID: 16828805)
معلومات مُعتمدة: G0400017 United Kingdom MRC_ Medical Research Council; J-0804 United Kingdom PUK_ Parkinson's UK
سلسلة جزيئية: ClinicalTrials.gov NCT00211224
المشرفين على المادة: 0 (SNCA protein, human)
0 (alpha-Synuclein)
تواريخ الأحداث: Date Created: 20090923 Date Completed: 20100201 Latest Revision: 20211020
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC2743996
DOI: 10.1371/journal.pone.0007114
PMID: 19771175
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0007114