title: α-Synuclein rs356219 polymorphisms in patients with Gaucher disease and Parkinson disease.
abstract: 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.
authors.affiliation: Genetics Unit, Shaare Zedek Medical Center, Affliated with the Hadassah-Hebrew University Medical School, Jerusalem, Israel.
authors.forename: Gheona
authors.initials: G
authors.lastname: Altarescu
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, Affliated with the Hadassah-Hebrew University Medical School, Jerusalem, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ioscovich
authors.affiliation: Department of Neurology and the Taub Institute, Columbia University Medical Center, New York, NY, USA.
authors.forename: Roy N
authors.initials: RN
authors.lastname: Alcalay
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, Affliated with the Hadassah-Hebrew University Medical School, Jerusalem, Israel.
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, Affliated with the Hadassah-Hebrew University Medical School, Jerusalem, Israel. Electronic address: elstein@szmc.org.il.
authors.forename: Deborah
authors.initials: D
authors.lastname: Elstein
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005776:Gaucher Disease / Q000208:ethnology / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007585:Jews; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein
keywords: Alpha-synuclein; Gaucher disease; Parkinson disease; Polymorphism