Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Comparison of Parkinson Risk in Ashkenazi Jewish Patients With Gaucher Disease and GBA Heterozygotes

Comparison of Parkinson Risk in Ashkenazi Jewish Patients With Gaucher Disease and GBA Heterozygotes ImportanceInformation on age-specific risk for Parkinson disease (PD) in patients with Gaucher disease (GD) and glucocerebrosidase (GBA) heterozygotes is important for understanding the pathophysiology of the genetic association and for counseling these populations. ObjectiveTo estimate the age-specific risk for PD in Ashkenazi Jewish patients with type 1 GD and in GBA heterozygotes. Design, Setting, and ParticipantsThe study included patients with GD from 2 tertiary centers, Shaare Zedek Medical Center, Jerusalem, Israel (n = 332) and Mount Sinai School of Medicine, New York, New York (n = 95). GBA noncarrier non-PD spouse control participants were recruited at the Center for Parkinson’s Disease at Columbia University, New York (n = 77). All participants were Ashekanzi Jewish and most patients (98.1%) with GD carried at least 1 N370S mutation. Main Outcomes and MeasuresThe main outcome measure was a diagnosis of PD. Diagnosis was established in patients with GD on examination. We used a validated family history interview that identifies PD with a sensitivity of 95.5% and specificity of 96.2% to identify PD in family members. Kaplan-Meier survival curves were used to estimate age-specific PD risk among patients with GD (n = 427), among their parents who are obligate GBA mutation carriers (heterozygotes, n = 694), and among noncarriers (parents of non-PD, non-GD control participants, n = 154). The age-specific risk was compared among groups using the log-rank test. ResultsAmong those who developed PD, patients with GD had a younger age at onset than GBA heterozygotes (mean, 54.2 vs 65.2 years, respectively; P = .003). Estimated age-specific risk for PD at 60 and 80 years of age was 4.7% and 9.1% among patients with GD, 1.5% and 7.7% among heterozygotes, and 0.7% and 2.1% among noncarriers, respectively. The risk for PD was higher in patients with GD than noncarriers (P = .008, log-rank test) and in heterozygotes than noncarriers (P = .03, log-rank test), but it did not reach statistical significance between patients with GD and GBA heterozygotes (P = .07, log-rank test). Conclusions and RelevancePatients with GD and GBA heterozygotes have an increased age-specific risk for PD compared with control individuals, with a similar magnitude of PD risk by 80 years of age; however, the number of mutant alleles may play an important role in age at PD onset. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Neurology American Medical Association

Comparison of Parkinson Risk in Ashkenazi Jewish Patients With Gaucher Disease and GBA Heterozygotes

Download PDF
6 pages

Loading next page...
 
/lp/american-medical-association/comparison-of-parkinson-risk-in-ashkenazi-jewish-patients-with-gaucher-fLcWmej8gd

References (32)

Publisher
American Medical Association
Copyright
Copyright 2014 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
ISSN
2168-6149
eISSN
2168-6157
DOI
10.1001/jamaneurol.2014.313
pmid
24756352
Publisher site
See Article on Publisher Site

Abstract

ImportanceInformation on age-specific risk for Parkinson disease (PD) in patients with Gaucher disease (GD) and glucocerebrosidase (GBA) heterozygotes is important for understanding the pathophysiology of the genetic association and for counseling these populations. ObjectiveTo estimate the age-specific risk for PD in Ashkenazi Jewish patients with type 1 GD and in GBA heterozygotes. Design, Setting, and ParticipantsThe study included patients with GD from 2 tertiary centers, Shaare Zedek Medical Center, Jerusalem, Israel (n = 332) and Mount Sinai School of Medicine, New York, New York (n = 95). GBA noncarrier non-PD spouse control participants were recruited at the Center for Parkinson’s Disease at Columbia University, New York (n = 77). All participants were Ashekanzi Jewish and most patients (98.1%) with GD carried at least 1 N370S mutation. Main Outcomes and MeasuresThe main outcome measure was a diagnosis of PD. Diagnosis was established in patients with GD on examination. We used a validated family history interview that identifies PD with a sensitivity of 95.5% and specificity of 96.2% to identify PD in family members. Kaplan-Meier survival curves were used to estimate age-specific PD risk among patients with GD (n = 427), among their parents who are obligate GBA mutation carriers (heterozygotes, n = 694), and among noncarriers (parents of non-PD, non-GD control participants, n = 154). The age-specific risk was compared among groups using the log-rank test. ResultsAmong those who developed PD, patients with GD had a younger age at onset than GBA heterozygotes (mean, 54.2 vs 65.2 years, respectively; P = .003). Estimated age-specific risk for PD at 60 and 80 years of age was 4.7% and 9.1% among patients with GD, 1.5% and 7.7% among heterozygotes, and 0.7% and 2.1% among noncarriers, respectively. The risk for PD was higher in patients with GD than noncarriers (P = .008, log-rank test) and in heterozygotes than noncarriers (P = .03, log-rank test), but it did not reach statistical significance between patients with GD and GBA heterozygotes (P = .07, log-rank test). Conclusions and RelevancePatients with GD and GBA heterozygotes have an increased age-specific risk for PD compared with control individuals, with a similar magnitude of PD risk by 80 years of age; however, the number of mutant alleles may play an important role in age at PD onset.

Journal

JAMA Neurology – American Medical Association

Published: Jun 1, 2014

There are no references for this article.