title: Variants in the SNCA gene associate with motor progression while variants in the MAPT gene associate with the severity of Parkinson's disease.
abstract: BACKGROUND
  It is well known that α-synuclein (SNCA) and microtubule associated protein (MAPT) genes predispose individuals to develop Parkinson's disease (PD). However, whether these genes contribute to differences in the variable progression observed in PD is obscure. This study aims to evaluate the association of common variants in SNCA (rs11931074, rs894278) and MAPT (rs242557_H1c haplotype, rs3744456) genes with the severity and duration of motor and cognitive performance.
  
  
  METHODS
  296 Chinese patients with PD were recruited from Shanghai Ruijin Hospital. Motor performance was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS-III) and Hoehn &Yahar (H&Y) stages and cognitive performance using the Mini-Mental Status Examination (MMSE). Genetic associations were analysed using general linear modelling for severity and Cox regression analysis for duration to motor (UPDRS-III≥36 or H&Y ≥ 3, average duration 13 years) and cognitive (MMSE<27, average duration 8 years) cutoffs, covarying for age and gender.
  
  
  RESULTS
  The severity of motor function associated with synergic interaction of SNCA (rs11931074) and MAPT (rs3744456) (p ≤ 0.05) while longer survival to the motor cutoff associated with SNCA (rs11931074/T, HR = 0.4, p = 0.03). Increased severity of cognitive function associated with MAPT (H1c haplotype, p = 0.05) with none of the risk alleles chosen associated with survival to the cognitive cutoff (p > 0.05).
  
  
  CONCLUSIONS
  Our findings add further data showing that common variants in SNCA and MAPT genes contribute to variability in progression of PD, with SNCA variants associating with motor progression while MAPT variants associated with clinical severity.
authors.affiliation: Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200025, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Neuroscience Research Australia & the University of New South Wales, Australia. Electronic address: yue.huang@unsw.edu.au.
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200025, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200025, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200025, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200025, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200025, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Movement Disorders Unit, Department of Neurology, Westmead Hospital & Sydney Medical School, University of Sydney, Australia.
authors.forename: Victor S C
authors.initials: VS
authors.lastname: Fung
authors.affiliation: Neuroscience Research Australia & the University of New South Wales, Australia.
authors.forename: Glenda
authors.initials: G
authors.lastname: Halliday
authors.affiliation: Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200025, China. Electronic address: chen_sd@medmail.com.cn.
authors.forename: Shengdi
authors.initials: S
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D012720:Severity of Illness Index; D055815:Young Adult; D051844:alpha-Synuclein / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins
keywords: Cognitive function; MAPT; Motor function; Parkinson's disease; SNCA