Evaluation of the Role of SNCA Variants in Survival without Neurological Disease 英文参考文献.docVIP

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Evaluation of the Role of SNCA Variants in Survival without Neurological Disease 英文参考文献.doc

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Evaluation of the Role of SNCA Variants in Survival without Neurological Disease 英文参考文献

EvaluationoftheRoleofSNCAVariantsinSurvival withoutNeurologicalDisease MichaelG.Heckman1*,AlexandraI.Soto-Ortolaza2,NancyN.Diehl1,MinervaM.Carrasquillo2, RyanJ.Uitti3,ZbigniewK.Wszolek3,NeillR.Graff-Radford3,OwenA.Ross2 1BiostatisticsUnit,MayoClinic,Jacksonville,Florida,UnitedStatesofAmerica,2DepartmentofNeuroscience,MayoClinic,Jacksonville,Florida,UnitedStatesofAmerica, 3DepartmentofNeurology,MayoClinic,Jacksonville,Florida,UnitedStatesofAmerica Abstract Background:Avarietyofdefinitionsofsuccessfulaginghavebeenproposed,manyofwhichrelatetolongevity,freedom from disease and disability, or preservation of high physical and cognitive function. Many behavioral, biomedical, and psychologicalfactorshavebeenlinkedwiththesevariousmeasuresofsuccessfulaging,howevergeneticpredictorsareless understood. Parkinson’s disease (PD) is an age-related neurodegenerative disorder, and variants in the a-synuclein gene (SNCA) affect susceptibility to PD. This exploratory study examined whether SNCA variants may also promote successful agingasdefinedbysurvivalwithoutneurologicaldisease. Methods:Weutilized769controlswithoutneurologicaldisease(Meanage:79years,Range:33–99years)andexaminedthe frequencyof20differentSNCAvariantsacrossagegroupsusinglogisticregressionmodels.Wealsoincluded426PDcases toassesstheeffectofthesevariantsonPDrisk. Results: There was a significant decline in the proportion of carriers of the minor allele of ras 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,wheretheproportionofcarriersoftheminoralleledeclinedfrom32%incontrolslessthan60yearsoldto19% in those 90 or older (P=0.025). A number of SNCA variants, not including ror rs3775439, were significantly associatedwithsusceptibilitytoPD. Conclusions:InadditiontoitsdocumentedrolesinPDanda-synucleinopathies,ourresultssuggestthatSNCAhasarolein survival freeof neurologicaldisease. Acknowledgingthat ourfindings w