Glucocerebrosidase Gene Mutations

Abstract

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. To better assess the role of GBA variants in altering risk for Lewy body disorders. Case-control study. Four movement disorder clinics in the Seattle, Washington, area. Seven hundred twenty-one patients with PD, 554 healthy control subjects, and 57 patients with DLB. Disease status and presence or absence of the 2 most common GBA mutations (N370S and L444P). 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%). 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.