The results of this study suggest that there may be an increased risk of developing PD in individuals with GLA mutations, but these findings should be interpreted with caution given the limitations of the study design.
Among women who were non-carriers of GBA and LRRK2 G2019S mutations (PD, n = 155; control, n = 194), alpha galactosidase A activity was lower in PD compared to controls (2.77 μmol/l/h versus 3.10 μmol/l/h, p = 0.044; after controlling for a batch effect, p = 0.001).
The lysosomal enzyme alpha-Galactosidase A is deficient in Parkinson's disease brain in association with the pathologic accumulation of alpha-synuclein.
Our data suggest that the sequence variant may affect GLA gene expression by altering transcription factor binding sites, contributing to the pathogenesis of sporadic PD.