Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews - PubMed (original) (raw)
Comparative Study
. 2004 Nov 4;351(19):1972-7.
doi: 10.1056/NEJMoa033277.
Affiliations
- PMID: 15525722
- DOI: 10.1056/NEJMoa033277
Free article
Comparative Study
Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews
Judith Aharon-Peretz et al. N Engl J Med. 2004.
Free article
Abstract
Background: A clinical association has been reported between type 1 Gaucher's disease, which is caused by a glucocerebrosidase deficiency owing to mutations in the glucocerebrosidase gene (GBA), and parkinsonism. We examined whether mutations in the GBA gene are relevant to idiopathic Parkinson's disease.
Methods: A clinic-based case series of 99 Ashkenazi patients with idiopathic Parkinson's disease, 74 Ashkenazi patients with Alzheimer's disease, and 1543 healthy Ashkenazi Jews who underwent testing to identify heterozygosity for certain recessive diseases were screened for the six GBA mutations (N370S, L444P, 84GG, IVS+1, V394L, and R496H) that are most common among Ashkenazi Jews.
Results: Thirty-one patients with Parkinson's disease (31.3 percent; 95 percent confidence interval, 22.2 to 40.4 percent) had one or two mutant GBA alleles: 23 were heterozygous for N370S, 4 were heterozygous for 84GG, 3 were homozygous for N370S, and 1 was heterozygous for R496H. Among the 74 patients with Alzheimer's disease, 3 were identified as carriers of Gaucher's disease (4.1 percent; 95 percent confidence interval, 0.0 to 8.5 percent): 2 were heterozygous for N370S, and 1 was heterozygous for 84GG. Ninety-five carriers of Gaucher's disease were identified among the 1543 control subjects (6.2 percent; 95 percent confidence interval, 5.0 to 7.4 percent): 92 were heterozygous for N370S, and 3 were heterozygous for 84GG. Patients with Parkinson's disease had significantly greater odds of being carriers of Gaucher's disease than did patients with Alzheimer's disease (odds ratio, 10.8; 95 percent confidence interval, 3.0 to 46.6; P<0.001) or control subjects (odds ratio, 7.0; 95 percent confidence interval, 4.2 to 11.4; P<0.001). Among the patients with Parkinson's disease, patients who were carriers of Gaucher's disease were younger than those who were not carriers (mean [+/-SD] age at onset, 60.0+/-14.2 years vs. 64.2+/-11.7 years; P=0.04).
Conclusions: Our results suggest that heterozygosity for a GBA mutation may predispose Ashkenazi Jews to Parkinson's disease.
Copyright 2004 Massachusetts Medical Society.
Comment in
- New genetic insights into Parkinson's disease.
Feany MB. Feany MB. N Engl J Med. 2004 Nov 4;351(19):1937-40. doi: 10.1056/NEJMp048263. N Engl J Med. 2004. PMID: 15525720 No abstract available. - The glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews.
Eblan MJ, Walker JM, Sidransky E. Eblan MJ, et al. N Engl J Med. 2005 Feb 17;352(7):728-31; author reply 728-31. doi: 10.1056/NEJM200502173520719. N Engl J Med. 2005. PMID: 15716572 No abstract available. - The glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews.
Schlossmacher MG, Cullen V, Müthing J. Schlossmacher MG, et al. N Engl J Med. 2005 Feb 17;352(7):728-31; author reply 728-31. N Engl J Med. 2005. PMID: 15719451 No abstract available. - The glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews.
Zimran A, Neudorfer O, Elstein D. Zimran A, et al. N Engl J Med. 2005 Feb 17;352(7):728-31; author reply 728-31. N Engl J Med. 2005. PMID: 15719452 No abstract available.
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