Sex effects on clinical features in LRRK2 G2385R carriers and non-carriers in Parkinson's disease

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Abstract Background Differences between male and female have been studied for PD but limited data was focused on the comparison between sexes with LRRK2 G2385 variant. Objective This study was to explore sex effects in the same genetic subtype and role of leucine-rich repeat kinase 2 (LRRK2) G2385R variants in the same sex. Methods 613 PD Patients were recruitment from Movement Disorders Clinic in Ruijin Hospital. Clinical data including demographic information, disease history, scales of motor and non-motor symptoms, midbrain transcranial sonography and DNA was collected. Binary logistic regression analysis was performed to evaluate the possible association between the clinical features and sex in LRRK2 G2385R carriers and non-carriers, and to evaluate the possible association between the clinical features and LRRK2 G2385R variants in male and female. Results Sex distribution is similar in LRRK2 G2385R carriers and non-carriers. In male sex, LRRK2 G2385R carriers showed lower risk in cognitive impairment compared with non-carriers (OR = 0.301, p = 0.003, 95%CI 0.135–0.668). In female sex, LRRK2 G2385R carriers showed lower risk in autonomic dysfunction compared with non-carrier (OR = 0.401, p = 0.040, 95%CI 0.167–0.960). In LRRK2 G2385R non-carriers, female showed lower risk of impairment in activity of daily living (OR = 0.610, P = 0.021, 95%CI 0.400-0.928), excessive daytime sleepiness (OR = 0.555, p = 0.007, 95%CI 0.361–0.853), substantia nigra hyperechogenicity (OR = 0.448, P = 0.019, 95%CI 0.228–0.878), autonomic dysfunction frequency (OR = 0.626, p = 0.016, 95%CI 0.428–0.917) and higher risk in mood disorders (OR = 1.691, p = 0.022, 95%CI (1.078–2.654) compared with male. In LRRK2 G2385R carriers, female showed a lower risk of autonomic dysfunction (OR = 0.294, p = 0.024, 95%CI 0.102–0.849) compared with male. Conclusion A more benign disease course was observed in female compared to male in both LRRK2 G2385R carriers and non-carriers. However, sex differences were less notable in PD with LRRK2 carriers.

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