The association between clinical phenotype of Parkinson’s disease and LRRK2 variants in China

Abstract Introduction: LRRK2 G2385R and LRRK2 S1647T have been identified as the most common risk variants for PD in the Chinese population. The aim of the study was to explore the correlation of LRRK2 G2385R, LRRK2 S1647T and their haplotypes with symptoms. Method: Demographic variables, disease-related variables and motor and non-motor assessments was collected in the study. Peripheral blood samples were collected, and DNA was extracted. SNaPShot technique was used to analysis DNA genotype. Chi square test and ANOVA was used to test the between-group differences. Risk analysis was performed by logistic regression model or Cochran-Armitage model. Results: 502 PD patients were enrolled in the study. The scores of PDSS and MoCA were significant higher in LRRK2 S1647T variants carriers genotype after adjustment. The scores of BPI, attention in NMSS, cardiovascular in SCOPA-AUT was significant lower in LRRK2 G2385R variants carriers adjusted for H-Y stage and gender. LRRK2 ARG 2385 was associated with reduced risk of sialorrhea (p=0.049, additive model) and postural hypotension (p=0.030, additive model; OR=0.35, 95%CI: 0.10-0.89, adjusted P=0.050, dominant model). rs11564148A rs34778348A was also found associated with a reduced risk with postural hypotension adjusted for H-Y staging and gender. Conclusion: Our study indicated that LRRK2 S1647T variants carriers presented better motor symptoms, sleep quality and cognition. LRRK2 G2385R variants carriers presented better autonomic function and cognition and had a reduced risk of sialorrhea and postural hypotension. rs11564148A - rs34778348A was associated with reduced risk with postural hypotension.