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PLOS ONE  2012 

Evaluation of the Role of SNCA Variants in Survival without Neurological Disease

DOI: 10.1371/journal.pone.0042877

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Abstract:

Background A variety of definitions of successful aging have been proposed, many of which relate to longevity, freedom from disease and disability, or preservation of high physical and cognitive function. Many behavioral, biomedical, and psychological factors have been linked with these various measures of successful aging, however genetic predictors are less understood. Parkinson's disease (PD) is an age-related neurodegenerative disorder, and variants in the α-synuclein gene (SNCA) affect susceptibility to PD. This exploratory study examined whether SNCA variants may also promote successful aging as defined by survival without neurological disease. Methods We utilized 769 controls without neurological disease (Mean age: 79 years, Range: 33–99 years) and examined the frequency of 20 different SNCA variants across age groups using logistic regression models. We also included 426 PD cases to assess the effect of these variants on PD risk. Results There was a significant decline in the proportion of carriers of the minor allele of rs10014396 as age increased (P = 0.021), from 30% in controls younger than 60 to 14% in controls 90 years of age or older. Findings were similar for rs3775439, where the proportion of carriers of the minor allele declined from 32% in controls less than 60 years old to 19% in those 90 or older (P = 0.025). A number of SNCA variants, not including rs10014396 or rs3775439, were significantly associated with susceptibility to PD. Conclusions In addition to its documented roles in PD and α-synucleinopathies, our results suggest that SNCA has a role in survival free of neurological disease. Acknowledging that our findings would not have withstood correction for multiple testing, validation in an independent series of aged neurologically normal controls is needed.

References

[1]  Harman D (1991) The aging process: major risk factor for disease and death. Proc Natl Acad Sci U S A 88: 5360–5363.
[2]  Kirkwood TB (1996) Human senescence. Bioessays 18: 1009–1016.
[3]  Karasik D, Demissie S, Cupples LA, Kiel DP (2005) Disentangling the genetic determinants of human aging: biological age as an alternative to the use of survival measures. J Gerontol A Biol Sci Med Sci 60: 574–587.
[4]  Rowe JW, Kahn RL (1987) Human aging: usual and successful. Science 237: 143–149.
[5]  Rowe JW, Kahn RL (1997) Successful aging. Gerontologist 37: 433–440.
[6]  Depp CA, Jeste DV (2006) Definitions and predictors of successful aging: a comprehensive review of larger quantitative studies. Am J Geriatr Psychiatry 14: 6–20.
[7]  Depp CA, Glatt SJ, Jeste DV (2007) Recent advances in research on successful or healthy aging. Curr Psychiatry Rep 9: 7–13.
[8]  de Lau LM, Breteler MM (2006) Epidemiology of Parkinson's disease. Lancet Neurol 5: 525–535.
[9]  Postuma RB, Montplaisir J (2009) Predicting Parkinson's disease - why, when, and how? Parkinsonism Relat Disord 15 Suppl 3: S105–109.
[10]  Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, et al. (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276: 2045–2047.
[11]  Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies. Proc Natl Acad Sci U S A 95: 6469–6473.
[12]  Spillantini MG, Schmidt ML, Lee VM, Trojanowsky JQ, Jakes R, et al. (1997) Alpha-synuclein in Lewy bodies. Nature 388: 839–840.
[13]  Ross OA, Braithwaite AT, Skipper LM, Kachergus J, Hulihan MM, et al. (2008) Genomic investigation of alpha-synuclein multiplication and parkinsonism. Ann Neurol 63: 743–750.
[14]  Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, et al. (2003) alpha-Synuclein locus triplication causes Parkinson's disease. Science 302: 841.
[15]  Ross OA, Gosal D, Stone JT, Lincoln SJ, Heckman MG, et al. (2007) Familial genes in sporadic disease: common variants of alpha-synuclein gene associate with Parkinson's disease. Mech Aging Dev 128: 378–382.
[16]  D?chsel JC, Lincoln SJ, Gonzalez J, Ross OA, Dickson DW, et al. (2007) The ups and downs of alpha-synuclein mRNA expression. Mov Disord 22: 293–295.
[17]  Elbaz A, Ross OA, Ioannidis JP, Soto-Ortolaza AI, Moisan F, et al. (2011) Independent and joint effects of the MAPT and SNCA genes in Parkinson disease. Ann Neurol 69: 778–792.
[18]  Mueller JC, Fuchs J, Hofer A, Zimprich A, Lichtner P, et al. (2005) Multiple regions of alpha-synuclein are associated with Parkinson's disease. Ann Neurol 57: 535–541.
[19]  Trotta L, Guella I, Soldà G, Sironi F, Tesei S, et al. (2012) SNCA and MAPT genes: Independent and joint effects in Parkinson disease in the Italian population. Parkinsomism Relat Disord 18: 257–262.
[20]  Graff-Radford NR, Ferman TJ, Lucas JA, Johnson HK, Parfitt FC, et al. (2006) A cost effective method of identifying and recruiting persons over 80 free of dementia or mild cognitive impairment. Alzheimer Dis Assoc Disord 20: 101–104.
[21]  Ross OA, Conneely KN, Wang T, Vilarino-Guell C, Soto-Ortolaza AI, et al. (2011) Genetic variants of α-synuclein are not associated with essential tremor. Mov Disord 26: 2552–2556.
[22]  Gelb DJ, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson disease. Arch Neurol 56: 33–39.
[23]  Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, et al. (2005) Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 15: 1034–1050.
[24]  Christensen K, Johnson TE, Vaupel JW (2006) The quest for genetic determinants of human longevity: challenges and insights. Nat Review Genet 7: 436–448.
[25]  Ross OA (2006) Longevics: genetic lessons for the ages. Ir J Med Sci 175: 82.
[26]  Glatt SJ, Chayavichitsilp P, Depp C, Schork NJ, Jeste DV (2007) Successful aging: from phenotype to genotype. Biol Psychiatry 62: 282–293.
[27]  Walter S, Atzmon G, Demerath EW, Garcia ME, Kaplan RC, et al. (2011) A genome-wide association study of aging. Neurobiol Aging 32: 2109.e15–28.
[28]  Wu SL, Wang WF, Shyu HY, Ho YJ, Shieh JC, et al. (2010) Association analysis of GRIN1 and GRIN2B polymorphisms and Parkinson's disease in a hospital-based case-control study. Neurosci Lett 478: 61–65.
[29]  Stein JL, Hua X, Morra JH, Lee S, Hibar DP, et al. (2010) Genome-wide analysis reveals novel genes influencing temporal lobe structure with relevance to neurodegeneration in Alzheimer's disease. Neuroimage 51: 542–554.
[30]  Nishioka K, Wider C, Vilari?o-Güell C, Soto-Ortolaza AI, Lincoln SJ, et al. (2010) Association of alpha-, beta-, and gamma-Synuclein with diffuse lewy body disease. Arch Neurol 67: 970–975.
[31]  Scholz SW, Houlden H, Schulte C, Sharma M, Li A, et al. (2009) SNCA variants are associated with increased risk for multiple system atrophy. Ann Neurol 65: 610–614.
[32]  Ross OA, Vilari?o-Güell C, Wszolek ZK, Farrer MJ, Dickson DW (2010) Reply to: SNCA variants are associated with increased risk of multiple system atrophy. Ann Neurol 67: 414–415.
[33]  Al-Chalabi A, Dürr A, Wood NW, Parkinson MH, Camuzat A, et al. (2009) Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy. PLoS One 4: e7114.

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