학술논문
Predictors of Parkin Mutations in Early-Onset Parkinson Disease: The Consortium on Risk for Early-Onset Parkinson Disease Study
Document Type
Academic Journal
Author
Marder, Karen S.; Tang, Ming X.; Mejia-Santana, Helen; Rosado, Llency; Louis, Elan D.; Comella, Cynthia L.; Colcher, Amy; Siderowf, Andrew D.; Jennings, Danna; Nance, Martha A.; Bressman, Susan; Scott, William K.; Tanner, Caroline M.; Mickel, Susan F.; Andrews, Howard F.; Waters, Cheryl; Fahn, Stanley; Ross, Barbara M.; Cote, Lucien J.; Frucht, Steven; Ford, Blair; Alcalay, Roy N.; Rezak, Michael; Novak, Kevin; Friedman, Joseph H.; Pfeiffer, Ronald F.; Marsh, Laura; Hiner, Brad; Neils, Gregory D.; Verbitsky, Miguel; Kisselev, Sergey; Caccappolo, Elise; Ottman, Ruth; Clark, Lorraine N.
Source
Archives of Neurology. Jun 01, 2010 67(6):731-738
Subject
Language
English
ISSN
0003-9942
Abstract
BACKGROUND: Mutations in the parkin gene are the most common genetic cause of early-onset Parkinson disease (PD). Results from a multicenter study of patients with PD systematically sampled by age at onset have not been reported to date. OBJECTIVE: To determine risk factors associated with carrying parkin mutations. DESIGN: Cross-sectional observational study. SETTING: Thirteen movement disorders centers. PARTICIPANTS: A total of 956 patients with early-onset PD, defined as age at onset younger than 51 years. MAIN OUTCOME MEASURES: Presence of heterozygous, homozygous, or compound heterozygous parkin mutations. RESULTS: Using a previously validated interview, 14.7% of patients reported a family history of PD in a first-degree relative. Sixty-four patients (6.7%) had parkin mutations (3.9% heterozygous, 0.6% homozygous, and 2.2% compound heterozygous). Copy number variation was present in 52.3% of mutation carriers (31.6% of heterozygous, 83.3% of homozygous, and 81.0% of compound heterozygous). Deletions in exons 3 and 4 and 255delA were common among Hispanics (specifically Puerto Ricans). Younger age at onset (<40 years) (odds ratio [OR], 5.0; 95% confidence interval [CI], 2.8-8.8; P = .001), Hispanic race/ethnicity (OR compared with white non-Hispanic race/ethnicity, 2.7; 95% CI, 1.3-5.7; P = .009), and family history of PD in a first-degree relative (OR compared with noncarriers, 2.8; 95% CI, 1.5-5.3; P = .002) were associated with carrying any parkin mutation (heterozygous, homozygous, or compound heterozygous). Hispanic race/ethnicity was associated with carrying a heterozygous mutation (OR compared with white non-Hispanic race/ethnicity, 2.8; 95% CI, 1.1-7.2; P = .03) after adjustment for covariates. CONCLUSIONS: Age at onset, Hispanic race/ethnicity, and family history of PD are associated with carrying any parkin mutation (heterozygous, homozygous, or compound heterozygous) and heterozygous mutations alone. The increased odds of carrying a parkin mutation among Hispanics warrants further study.