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

• This is the first genetic study demonstrating genes predicating the progression of Parkinson's disease in Chinese patients.
• Motor performance was assessed using UPDRS and H&Y stages and cognitive performance using MMSE.
• Genetic associations with the severity of Parkinson's disease and with duration to motor and cognitive cutoffs were analysed.
• Variants in SNCA and MAPT genes contribute to the survival and the severity of motor dysfunction in Parkinson's disease.
• MAPT H1c haplotype weakly associates with cognitive severity, but not associated with survival to the cognitive cutoff.

IntroductionIt 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.Methods296 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.ResultsThe 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).ConclusionOur 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.