A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies
A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies
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DOI：
10.1001/jamaneurol.2013.1925
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发表时间：
2013-06-01
期刊：
影响因子：
29
通讯作者：
Sidransky, Ellen
中科院分区：
文献类型：
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作者：
Nalls, Michael A.;Duran, Raquel;Sidransky, Ellen
重要性：虽然葡萄糖脑苷酶（GBA1）突变与帕金森病（PD）风险增加相关，但确定这种突变是否也是其他路易体疾病的常见危险因素是很重要的。目的：探讨GBA1突变是否为路易体痴呆（DLB）的危险因素。设计：我们比较了来自11个中心的患者和对照组的基因型数据。收集有关人口统计学、发病年龄、病程、临床和病理特征的资料。我们使用逻辑回归进行了汇总分析，研究GBA1突变携带者状态对DLB或PD合并痴呆状态的预测作用，并以普通对照组为参照组。进行随机效应荟萃分析以解释额外的异质性。环境：来自世界各地的11个中心进行基因分型。参与者：721例符合DLB诊断标准，151例PD伴痴呆。我们将这些病例与1962年来自相同中心的年龄、性别和种族相匹配的对照进行比较。主要观察指标：病例和对照组中GBA1突变的频率。结果：我们发现GBA1突变携带者状态与DLB之间存在显著相关性，优势比为8.28 （95% CI, 4.78-14.88）。PD合并痴呆的优势比为6.48 （95% CI, 2.53-15.37）。GBA1突变携带者比非携带者诊断DLB的平均年龄更早（63.5岁vs 68.9岁；P < 0.001），疾病严重程度评分更高。结论和相关性：GBA1突变是DLB的重要危险因素。GBA1突变可能在DLB的遗传病因中比在PD中发挥更大的作用，为糖脑苷酶在路易体病中的作用提供了新的见解。
Importance: While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders.Objective: To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB).Design: We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate GBA1 mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity.Setting: Eleven centers from sites around the world performing genotyping.Participants: Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity.Main Outcome Measures: Frequency of GBA1 mutations in cases and controls.Results: We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78-14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53-15.37). The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years; P < .001), with higher disease severity scores.Conclusions and Relevance: Mutations in GBA1 are a significant risk factor for DLB. GBA1 mutations likely play an even larger role in the genetic etiology of DLB than in PD, providing insight into the role of glucocerebrosidase in Lewy body disease.