Mutations in the glucocerebrosidase gene are associated with early-onset Parkinson disease
Mutations in the glucocerebrosidase gene are associated with early-onset Parkinson disease
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DOI：
10.1212/01.wnl.0000276989.17578.02
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发表时间：
2007-09-18
期刊：
影响因子：
9.9
通讯作者：
Marder, K.
中科院分区：
文献类型：
--
作者：
Clark, L. N.;Ross, B. M.;Marder, K.
目的：为了评估的频率葡萄糖脑苷脂酶（GBA）突变的情况下，对照组的遗传流行病学帕金森病（GEPD）study.Methods：我们测序的GBA基因的所有外显子在278帕金森病（PD）的情况下，179名对照组在GEPD，发病年龄（AAO）的范围很广，其中包括一个子集的178例犹太人和85犹太人对照。结果：13.7%的PD病例（38/278）携带GBA突变，对照组携带GBA突变的比例为4.5%（8/179）（优势比[OR] 3.4，95%CI 1.5 ~ 7.4）。在90例年龄> 50岁的AAO患者中，GBA突变频率为22.2%（OR 2.7，95% CI 1.3 ~ 5.3）。调整评估时的年龄、性别、PD家族史和犹太血统，GBA携带者比非携带者的PD AAO早1.7年（95%CI 0.5 - 3.3，p < 0.04）。在AAO 50岁组的携带者中，PD的平均AAO提前2.5年。在178例报告有4名犹太祖父母的病例中，GBA突变频率（16.9%）高于未报告犹太血统的病例（8.0%）（P < 0.01）。在PD患者中检测到9种不同的GBA突变，包括84 insGG、E326 K、T369 M、N370 S、D409 H、R496 H、L444 P、RecN 1和一种新的突变P175 P。结论：葡萄糖脑苷脂酶基因可能是帕金森病的易感基因，葡萄糖脑苷脂酶突变可能改变帕金森病的发病年龄。
Objective: To evaluate the frequency of glucocerebrosidase (GBA) mutations in cases and controls enrolled in the Genetic Epidemiology of Parkinson's Disease (GEPD) study.Methods: We sequenced all exons of the GBA gene in 278 Parkinson disease (PD) cases and 179 controls enrolled in GEPD, with a wide range of age at onset (AAO), and that included a subset of 178 Jewish cases and 85 Jewish controls. Cases and controls were recruited without knowledge of family history of PD, and cases were oversampled in the AAO < 50 years category.Results: 13.7% of PD cases (38/278) carried GBA mutations, compared with 4.5% of controls (8/179) (odds ratio [OR] 3.4, 95% Cl 1.5 to 7.4). The frequency of GBA mutations was 22.2% in 90 cases with AAO 50 years (OR 2.7, 95% Cl 1.3 to 5.3). Adjusting for age at the time of evaluation, sex, family history of PD, and Jewish ancestry, GBA carriers had a 1.7-year-earlier AAO of PD (95% Cl 0.5 to 3.3, p < 0.04) than noncarriers. The average AAO of PD was 2.5 years earlier in carriers with an AAO 50 years group. The frequency of GBA mutations was higher in a subset of 178 cases that reported four Jewish grandparents (16.9%) than in cases who did not report Jewish ancestry (8.0%) (P < 0.01). Nine different GBA mutations were identified in PD cases, including 84insGG, E326K, T369M, N370S, D409H, R496H, L444P, RecNcil, and a novel mutation, P175P.Conclusions: This study suggests that the Glucocerebrosidase gene may be a susceptibility gene for Parkinson disease and that Glucocerebrosidase mutations may modify age at onset.