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From the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain (L.N.C., E.D.L., K.M.), Departments of Pathology (L.N.C., E.K., L.S.), Neurology (J.H., E.D.L., L.J.C., S.F., C.W., B.F., S.F., R.O., K.M.), and Psychiatry (H.A., K.M.), and the G.H. Sergievsky Center (H.M.-S., E.D.L., L.J.C., H.A., R.O., K.M.), College of Physicians and Surgeons, Department of Biostatistics (Y.W.), Department of Epidemiology (R.O.), Mailman School of Public Health, Columbia University, New York, NY; and Epidemiology of Brain Disorders Department (K.M.), New York State Psychiatric Institute, New York.
Address correspondence and reprint requests to Dr. Lorraine N. Clark; Department of Pathology, Columbia University, P&S Building, 14-434, 630 West 168th Street, New York, NY 10032; e-mail: lc654{at}columbia.edu
Objective: To evaluate the frequency of leucine-rich repeat kinase gene (LRRK2) mutations and single nucleotide polymorphisms (SNPs) in early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD).
Methods: We genotyped five previously reported LRRK2 mutations (G2019S, L1114L, I1122V, R1441C, and Y1699C) and 17 coding SNPs for haplotype analysis in 504 cases with PD and 314 controls enrolled in the Genetic Epidemiology of PD Study. Cases and controls were recruited without knowledge of family history of PD and cases were oversampled in the 
50 age at onset (AAO) category.
Results: The LRRK2 G2019S mutation was present in 28 cases with PD (5.6%) and two controls (0.6%) (
2 = 13.25; p < 0.01; odds ratio 9.18, 95% CI: 2.17 to 38.8). The mutations L1114L, I1122V, R1441C, and Y1699C were not identified. The frequency of the LRRK2 G2019S mutation was 4.9% in 245 cases with AAO 50 years vs 6.2% in 259 cases with AAO >50 (p = 0.56). All cases with PD with the G2019S mutation shared the same disease-associated haplotype. The frequency of the LRRK2 G2019S mutation was higher in the subset of 181 cases reporting four Jewish grandparents (9.9%) than in other cases (3.1%) (p < 0.01). Age-specific penetrance to age 80 was 24% and was similar in Jewish and non-Jewish cases.
Conclusions: The G2019S mutation is a risk factor in both early- and late-onset Parkinson disease and confirms the previous report of a greater frequency of the G2019S mutation in Jewish than in non-Jewish cases with Parkinson disease.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the November 28 issue to find the title link for this article.
This article was previously published in electronic format as an Expedited E-Pub on October 18, 2006, at www.neurology.org.
Funded by the PD Foundation to L.N.C, and K.M. and the National Institutes of Health (grants NS36630 and RR00645) to K.M.
Disclosure: The authors report no conflicts of interest.
Received March 30, 2006. Accepted in final form July 21, 2006.
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