Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders.
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.


METHODS
Case-control study.


METHODS
Four movement disorder clinics in the Seattle, Washington, area.


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


METHODS
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%).


CONCLUSIONS
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.
Mata
Ignacio F
IF
Department of Neurology, University of Washington School of Medicine, Seattle, USA.
Samii
Ali
A
Schneer
Seth H
SH
Roberts
John W
JW
Griffith
Alida
A
Leis
Berta C
BC
Schellenberg
Gerard D
GD
Sidransky
Ellen
E
Bird
Thomas D
TD
Leverenz
James B
JB
Tsuang
Debby
D
Zabetian
Cyrus P
CP
D000368:Aged; D001216:Asparagine / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D007930:Leucine / Q000235:genetics; D020961:Lewy Body Disease / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics; D011392:Proline / Q000235:genetics; D012307:Risk Factors; D012694:Serine / Q000235:genetics
D012694:Serine; D001216:Asparagine; D011392:Proline; D005962:Glucosylceramidase; D007930:Leucine