Gang Wang1, Yue Huang2, Wei Chen1, Shuai Chen1, Ying Wang1, Qin Xiao1, Jun Liu1, Victor S C Fung3, Glenda Halliday4, Shengdi Chen5. 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.
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.
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.
Authors: Koji Kasanuki; Michael G Heckman; Nancy N Diehl; Melissa E Murray; Shunsuke Koga; Alexandra Soto; Owen A Ross; Dennis W Dickson Journal: Mov Disord Date: 2017-09-26 Impact factor: 10.338
Authors: Esterina Pascale; Maria Elena Di Battista; Alfonso Rubino; Carlo Purcaro; Marcella Valente; Francesco Fattapposta; Giampiero Ferraguti; Giuseppe Meco Journal: Front Cell Neurosci Date: 2016-04-11 Impact factor: 5.505
Authors: Clarissa L C Campêlo; Fernanda C Cagni; Diego de Siqueira Figueredo; Luiz G Oliveira; Antônio B Silva-Neto; Priscila T Macêdo; José R Santos; Geison S Izídio; Alessandra M Ribeiro; Tiago G de Andrade; Clécio de Oliveira Godeiro; Regina H Silva Journal: Front Aging Neurosci Date: 2017-06-20 Impact factor: 5.750