Glucocerebrosidase gene mutations - A risk factor for Lewy body disorders

被引：157

作者：

Mata, Ignacio F. ^{[1
,4
]}

Samii, Ali ^{[3
,4
]}

Schneer, Seth H. ^{[9
]}

Roberts, John W. ^{[5
]}

Griffith, Alida ^{[10
]}

Leis, Berta C. ^{[10
]}

Schellenberg, Gerard D. ^{[1
,4
,6
,7
]}

Sidransky, Ellen ^{[11
]}

Bird, Thomas D. ^{[1
,4
,6
]}

Leverenz, James B. ^{[2
,3
,4
,8
]}

Tsuang, Debby ^{[2
,8
]}

Zabetian, Cyrus P. ^{[1
,2
,3
,4
]}

机构：

[1] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA

[2] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA

[3] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA

[4] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA

[5] Virginia Mason Med Ctr, Seattle, WA 98101 USA

[6] Univ Washington, Dept Med, Seattle, WA USA

[7] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA

[8] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA

[9] Oberlin Coll, Dept Biol, Oberlin, OH 44074 USA

[10] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA

[11] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA

来源：

ARCHIVES OF NEUROLOGY | 2008年 / 65卷 / 03期

关键词：

D O I：

10.1001/archneurol.2007.68

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：379 / 382

页数：4

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