The Gender Effect In The Risk And Manifestation Of Leucine-rich Repeat Kinase 2 Associated Parkinson Disease

Objective: The gender effect in the manifestation of leucine-rich repeat kinase 2(LRRK2)associated Parkinson disease(PD)remains controversial.Herein,we conducted a meta-analysis and a retrospective study to investigate the gender effect among these patients.Materials and methods: To investigate the gender effect in development of LRRK2-associated PD,PubMed and EMBASE databases were searched to identify the potential related studies published before December 2017.Studies met our criteria were included in further analyses.Meanwhile quality assessment was performed.We pooled relative risks(RRs)and 95% Confidence interval(CI)using fixed-effect model.The heterogeneity were assessed the publication bias and sensitivity analyses were also performed.To discuss the gender differences in clinical manifestations among patients with LRRK2-associated PD,we performed a retrospective study of patients,who diagnosed of PD in our clinic between May,2015 and May,2017.We described their basic characteristics,grouped them by carried variants or not and discussed their differences by T test,Rank-sum test,Chi-squared Test and Fisher exact test.Results: Sixty-four studies with 32452 patients diagnosed with PD were included.Higher prevalence of female patients with LRRK2-associated PD was observed with a pooled RR of 1.22(95% CI 1.14–1.30,P<0.001).Further subgroup analyses showed that higher prevalence of female patients was only obtained in G2019 S mutation patients(RR=1.32,95% CI 1.23–1.43,P < 0.001),but not in G2385 R variant patients(RR=1.03,95% CI 0.91–1.17,P=0.651).No significant heterogeneity and publication bias were observed in additional analyses.Retrospect study of 141 PD patients showed risk increased in female patients who carried G2385 R variants.However we pooled the relative risks with former result,no gender difference shown in risk of developing PD in G2385 R carriers.In the carriers of G2385 R variants,PIGD type(46.67%)showed predominantly in female patients while TD type(60.00%)was mainly seen male patients.Male carriers had lower score in UPDRS-II and PIGD subgroup which indicated better performance in daily activityabilities and gait and posture compared with non-carriers.Conclusions: Higher female prevalence of LRRK2 mutation suggests roles of gender-related risk factors in PD patients,especially who carried G2019 S mutation.Contrary to idiopathic PD,no sex difference was observed in prevalence of patients carried G2385 R variant.Male carriers show better performance in their daily activities as well as gait and posture.Our results revealed that gender related risk factors played a part in development and progression in LRRK2-associated PD.