2. Academic Validation
  3. Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders

Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders

  • Arch Neurol. 2008 Mar;65(3):379-82. doi: 10.1001/archneurol.2007.68.
Ignacio F Mata 1,  Ali Samii,  Seth H Schneer,  John W Roberts,  Alida Griffith,  Berta C Leis,  Gerard D Schellenberg,  Ellen Sidransky,  Thomas D Bird,  James B Leverenz,  Debby Tsuang,  Cyrus P Zabetian
Affiliations

Affiliation

  • 1 Department of Neurology, University of Washington School of Medicine, Seattle, USA.
PMID: 18332251 DOI: 10.1001/archneurol.2007.68
Abstract

Background: Mutations in the glucocerebrosidase (GBA) gene have been reported to modify risk for Parkinson disease (PD) and dementia with Lewy bodies (DLB). However, these findings have not been consistently replicated, and most studies have had substantial methodological shortcomings.

Objective: To better assess the role of GBA variants in altering risk for Lewy body disorders.

Design: Case-control study.

Setting: Four movement disorder clinics in the Seattle, Washington, area.

Participants: Seven hundred twenty-one patients with PD, 554 healthy control subjects, and 57 patients with DLB.

Main outcome measures: Disease status and presence or absence of the 2 most common GBA mutations (N370S and L444P).

Results: We observed a significantly higher heterozygote frequency for the 2 mutations in patients with PD (2.9%; P <.001) and those with DLB (3.5%; P = .045) compared with control subjects (0.4%).

Conclusion: Our findings suggest that GBA mutations exert a large effect on susceptibility for Lewy body disorders at the individual level but are associated with a modest (approximately 3%) population-attributable risk in individuals of European ancestry.

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