α-Synuclein rs356219 polymorphisms in patients with Gaucher disease and Parkinson disease

•Gaucher disease (GD) mutations increase risk of Parkinson disease (PD).•α-synuclein polymorphisms correlate with early-onset type PD seen in GD + PD patients.•Major (A): minor (G) allele frequency in GD + PD (17:11) and GD (19:9) is comparable.•Limitation of this study is few GD + PD patients (14/500 adult patients in clinic).•No difference between GD + PD and GD controls for α-synuclein rs356219 allele frequency.

Mutations in β-glucocerebrosidase, the genetic defect in Gaucher disease (GD), are an important susceptibility factor for Parkinson disease (PD). A PD effector is α-synuclein (SNCA) hypothesized to selectively interact with β-glucocerebrosidase under lysosomal conditions. SNCA polymorphism rs356219 may be associated with early-age-onset PD, common among patients with GD + PD. The objective of this study was to ascertain rs356219 genotypes of GD + PD patients. All GD + PD patients at our Gaucher referral clinic were asked to participate. A GD-only sex-, age-, GD genotype-, and enzyme therapy (ERT)-matched control was found for each GD + PD participant. Student's t-test was used (p-value <0.05 as significant). There were 14 GD + PD patients: all Ashkenazi Jewish; 11 males (78.6%); mean (range) age diagnosed GD 34.2 (5–62) years; 50% N370S homozygous; mild to moderate GD; 3 asplenic and only these have osteonecrosis; 5 received ERT; mean age (range) diagnosed PD was 57.8 (43–70) years; first PD sign was tremor in 9 (64.3%); cognitive dysfunction in all. In GD + PD, frequency for AG + GG (9) was greater than AA (5); in GD only, there was equality (7). Odds Ratio risk for PD increases with number minor alleles: but not significantly greater among GD + PD than GD only; in aggregate, there was no difference between cohorts for frequency of minor alleles. The limitation of this study is few GD + PD, albeit virtually all the GD + PD cohort >500 adult GD patients in our clinic. Nonetheless, as a foray into potential genetic GD susceptibility for a synucleinopathy, this study suggests the need for collaboration to achieve larger sample size.