Variants in the SNCA gene associate with motor progression while variants in the MAPT gene associate with the severity of Parkinson's disease

Gang Wang; Yue Huang; Wei Chen; Shuai Chen; Ying Wang; Qin Xiao; Jun Liu; Victor S C Fung; Glenda Halliday; Shengdi Chen

doi:10.1016/j.parkreldis.2015.12.018

Variants in the SNCA gene associate with motor progression while variants in the MAPT gene associate with the severity of Parkinson's disease

Parkinsonism Relat Disord. 2016 Mar:24:89-94. doi: 10.1016/j.parkreldis.2015.12.018. Epub 2015 Dec 30.

Authors

Gang Wang¹, Yue Huang², Wei Chen¹, Shuai Chen¹, Ying Wang¹, Qin Xiao¹, Jun Liu¹, Victor S C Fung³, Glenda Halliday⁴, Shengdi Chen⁵

Affiliations

¹ Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 200025, China.
² Neuroscience Research Australia & the University of New South Wales, Australia. Electronic address: yue.huang@unsw.edu.au.
³ Movement Disorders Unit, Department of Neurology, Westmead Hospital & Sydney Medical School, University of Sydney, Australia.
⁴ Neuroscience Research Australia & the University of New South Wales, Australia.
⁵ 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.

PMID: 26776090
DOI: 10.1016/j.parkreldis.2015.12.018

Abstract

Introduction: 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).

Conclusion: 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.

Keywords: Cognitive function; MAPT; Motor function; Parkinson's disease; SNCA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Child
Child, Preschool
Cognition Disorders / etiology
DNA Mutational Analysis
Disease Progression
Female
Genetic Association Studies
Genotype
Humans
Infant
Kaplan-Meier Estimate
Male
Neuropsychological Tests
Parkinson Disease / genetics*
Parkinson Disease / physiopathology*
Polymorphism, Single Nucleotide / genetics*
Regression Analysis
Severity of Illness Index
Young Adult
alpha-Synuclein / genetics*
tau Proteins / genetics*

Substances

MAPT protein, human
SNCA protein, human
alpha-Synuclein
tau Proteins