Journal of Inherited Metabolic Disease

, Volume 36, Issue 3, pp 575–580 | Cite as

Greater risk of parkinsonism associated with non-N370S GBA1 mutations

  • M. J. Barrett
  • P. Giraldo
  • J. L. Capablo
  • P. Alfonso
  • P. Irun
  • B. Garcia-Rodriguez
  • M. Pocovi
  • G. M. Pastores
Original Article

Abstract

Mutations in β-glucosidase (GBA1) are the most common genetic risk factor for Parkinson disease (PD). There is evidence to suggest that PD risk is greater (1) in GBA1 heterozygotes with non-N370S GBA1 mutations compared to N370S mutations and (2) in GD type 1 (GD1) patients compared to GBA1 heterozygotes. This study aimed to determine the comparative risk of parkinsonism in individuals who are affected or carriers of Gaucher disease (GD) and to ascertain the influence of different GBA1 mutations on risk/clinical expression. We conducted a secondary analysis of cross-sectional data assessing the prevalence of parkinsonism in a population of GD1 patients and their heterozygote and non-carrier family members. Two logistic regression models, both employing a family-specific random effect, were used to assess (1) the association between GBA1 mutation (N370S or non-N370S) and parkinsonism among GBA1 heterozygotes and (2) the association between GBA1 genotype and parkinsonism. Parkinsonism was present in 8.6 % of GD1 (7/81), 8.7 % of GBA1 heterozygotes (18/207), and 2.2 % of non-carriers (1/45). For those greater than 60 years old, parkinsonism was present in 38.5 % (5/13) of GD1 (5/13), 15.3 % of GBA1 heterozygotes (13/85), and 7.1 % of non-carriers (1/14). Among GBA1 heterozygotes, non-N370S mutations were associated with a significantly increased risk of parkinsonism compared to N370S (OR = 22.5; p = 0.035; 95%CI: 1.24, 411). In this population, each additional GBA1 mutation was associated with a non-significant two-fold increased risk of parkinsonism. GBA1 heterozygotes with non-N370S mutations associated with Gaucher disease have an increased risk of parkinsonism compared to those with N370S mutations.

Supplementary material

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ESM 1(DOC 332 kb)

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Copyright information

© SSIEM and Springer 2012

Authors and Affiliations

  • M. J. Barrett
    • 1
  • P. Giraldo
    • 2
    • 3
    • 4
  • J. L. Capablo
    • 5
  • P. Alfonso
    • 2
    • 3
    • 4
  • P. Irun
    • 2
    • 3
  • B. Garcia-Rodriguez
    • 4
  • M. Pocovi
    • 3
    • 6
  • G. M. Pastores
    • 7
  1. 1.Department of NeurologyBeth Israel Medical CenterNew YorkUSA
  2. 2.Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)ZaragozaSpain
  3. 3.Instituto de Investigación Sanitaria de Aragón (IIS)ZaragozaSpain
  4. 4.Translational Research UnitMiguel Servet University HospitalZaragozaSpain
  5. 5.Neurology DepartmentMiguel Servet University HospitalZaragozaSpain
  6. 6.Departamento de Bioquímica y Biología Molecular y CelularUniversidad de ZaragozaZaragozaSpain
  7. 7.Department of Neurology, Neurogenetics UnitNYU Langone Medical CenterNew YorkUSA

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