SNCA Variants Are Associated with Increased Risk for Multiple System Atrophy

Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA.
Annals of Neurology (Impact Factor: 11.91). 05/2009; 65(5):610-4. DOI: 10.1002/ana.21685
Source: PubMed

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].

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Available from: Reema Paudel, Aug 16, 2015
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    • "So far, no SNCA mutations were reported for MSA, while a MSA-like phenotype was described in one case with SNCA duplication (Fuchs et al., 2007). Several polymorphisms at the SNCA locus were linked to both idiopathic PD and MSA (Al-Chalabi et al., 2009; Nalls et al., 2011; Scholz et al., 2009). Additional polymorphisms of the tau gene and others were identified for PD, but not for MSA which could either be related to different pathogenesis or to the insufficient power of the MSA studies due to the small number of included patients. "
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    Neurobiology of Disease 07/2014; 67. DOI:10.1016/j.nbd.2014.03.021 · 5.20 Impact Factor
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    • "MSA is rarely familial (Soma et al., 2006) and mutations in a-synuclein have not been observed (Ozawa et al., 2006). However , polymorphisms in the synuclein gene may influence susceptibility to MSA (Al-Chalabi et al., 2009; Scholz et al., 2009). "
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    ABSTRACT: Human genetics has indicated a causal role for the protein α-synuclein in the pathogenesis of familial Parkinson's disease (PD), and the aggregation of synuclein in essentially all patients with PD suggests a central role for this protein in the sporadic disorder. Indeed, the accumulation of misfolded α-synuclein now defines multiple forms of neural degeneration. Like many of the proteins that accumulate in other neurodegenerative disorders, however, the normal function of synuclein remains poorly understood. In this article, we review the role of synuclein at the nerve terminal and in membrane remodeling. We also consider the prion-like propagation of misfolded synuclein as a mechanism for the spread of degeneration through the neuraxis.
    Neuron 09/2013; 79(6):1044-66. DOI:10.1016/j.neuron.2013.09.004 · 15.98 Impact Factor
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    • "Some cases with disease-causing mutations in SNCA exhibit neuropathological characteristics of both PD and MSA [27] [28] [29] [30]. Sequence variation in SNCA is a risk factor for MSA, which is largely a sporadic disease [31] [32]. It follows that therapies targeting the abnormal aggregation of α-synuclein are also likely to be effective in MSA. "
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    ABSTRACT: The definition of Parkinson's disease (PD) is changing with the expansion of clinical phenomenology and improved understanding of environmental and genetic influences that impact on the pathogenesis of the disease at the cellular and molecular level. This had led to debate and discussion with as yet, no general acceptance of the direction that change should take either at the level of diagnosis or of what should and should not be sheltered under an umbrella of PD. This article is one contribution to this on-going discussion. There are two different themes running through the article - widening the definition of PD/LBD/synucleinopathies and the heterogeneity that exists within PD itself from a clinical, pathological and genetic perspective. The conclusion reached is that in the future, further diagnostic categories will need to be recognized. These are likely to include - Parkinson's syndrome, Parkinson's syndrome likely to be Lewy body PD, clinical PD (defined by QSBB criteria), Lewy body disease (PD, LBD, REM SBD) and synucleinopathies (including LBD, MSA).
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