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
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, 630 W 168th St, Unit 16, New York, NY 10032, USA.
Arch Neurol. 2010 Jun;67(6):731-8. doi: 10.1001/archneurol.2010.95.
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.
To determine risk factors associated with carrying parkin mutations.
Cross-sectional observational study.
Thirteen movement disorders centers.
A total of 956 patients with early-onset PD, defined as age at onset younger than 51 years.
Presence of heterozygous, homozygous, or compound heterozygous parkin mutations.
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.
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.
帕金森病基因（parkin）突变是早发性帕金森病（PD）最常见的遗传病因。迄今为止，尚未有关于按发病年龄系统抽样的PD患者多中心研究结果的报道。
确定与携带parkin基因突变相关的危险因素。
横断面观察性研究。
13个运动障碍中心。
共有956例早发性PD患者，定义为发病年龄小于51岁。
杂合、纯合或复合杂合parkin基因突变的存在情况。
通过先前验证的访谈，14.7%的患者报告一级亲属中有PD家族史。64例患者（6.7%）存在parkin基因突变（3.9%为杂合，0.6%为纯合，2.2%为复合杂合）。52.3%的突变携带者存在拷贝数变异（杂合携带者中为31.6%，纯合携带者中为83.3%，复合杂合携带者中为81.0%）。外显子3和4的缺失以及255delA在西班牙裔（特别是波多黎各人）中很常见。发病年龄较小（<40岁）（比值比[OR]，5.0；95%置信区间[CI]，2.8 - 8.8；P = .001）、西班牙裔种族/族裔（与非西班牙裔白人种族/族裔相比，OR为2.7；95% CI，1.3 - 5.7；P = .009）以及一级亲属中有PD家族史（与非携带者相比，OR为2.8；95% CI，1.5 - 5.3；P = .002）与携带任何parkin基因突变（杂合、纯合或复合杂合）相关。在对协变量进行调整后，西班牙裔种族/族裔与携带杂合突变相关（与非西班牙裔白人种族/族裔相比，OR为2.8；95% CI，1.1 - 7.2；P = .03）。
发病年龄、西班牙裔种族/族裔以及PD家族史与携带任何parkin基因突变（杂合、纯合或复合杂合）以及单独的杂合突变相关。西班牙裔人群中携带parkin基因突变的几率增加值得进一步研究。
