Differences in Sex‐Specific Frequency of Glucocerebrosidase Variant Carriers and Familial Parkinsonism

Abstract

One sample binominal test was performed to assess proportions of different genders in the Serbian GBA-PD cohort overall and subgroups based on variant status. Severe GBA mutations were more frequent in women, while risk variants were more frequent among men. However, a statistically significant difference was not reached in any of the tested subgroups (Table 1). Our results for a Serbian cohort of patients with PD failed to confirm sex-specific inequal frequencies of GBA variants based on their severity. Moreover, the most frequently detected mutations in our GBA-PD cohort were severe, in contrast with findings of Ortega and colleagues, 1 where the mild mutations were the most frequent.Observed differences between our cohort and the cohort analyzed by Ortega et al 1 could be a consequence of selection bias or just an illustration that the frequency and distribution of GBA mutations vary among populations. 4 True frequency of GBA variants in both studies might be underestimated because of sequencing of only selected GBA exons. Therefore, larger studies in various ethnic populations using sequencing of all GBA exons will be required to enlighten potential sexspecific distribution of GBA variants.

Differences in Sex‐Specific Frequency of Glucocerebrosidase Variant Carriers and Familial Parkinsonism

“…However, this was not statistically significant at their sample size and would require a larger sample to demonstrate a statistically significant effect. In contrast, the report from Thaler et al 2 showed opposite sex‐specific frequencies. These interesting discrepancies underline the pressing need, highlighted by both groups and a core conclusion of our paper, to further evaluate in larger ongoing studies sex dimorphisms in genotypic‐phenotypic associations and to continue to report additional cases in a diversity of studies and ethnicities worldwide to better understand sex differences in PD.…”

“…We are grateful for the responses of Kresojević et al 1 analyzing Serbian cohorts and Thaler et al 2 analyzing Israeli cohorts that further expand the literature describing sex differences in Parkinson's disease (PD) associated with leucine‐rich repeat kinase 2 ( LRRK2 ) and glucocerebrosidase ( GBA ) variants. These two studies provide international data consistent with our and others' reports of a similar sex frequency in GBA PD and idiopathic PD with overall 60 men:40 women compared to no sex differences in frequency of LRRK2 G2019S PD 2,3 …”