Optimal Plasma Progranulin Cutoff Value for Predicting Null Progranulin Mutations in Neurodegenerative Diseases: A Multicenter Italian Study
Optimal Plasma Progranulin Cutoff Value for Predicting Null Progranulin Mutations in Neurodegenerative Diseases: A Multicenter Italian Study
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DOI：
10.1159/000333132
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发表时间：
2012-01-01
影响因子：
3
通讯作者：
Benussi, Luisa
中科院分区：
文献类型：
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作者：
Ghidoni, Roberta;Stoppani, Elena;Benussi, Luisa
背景：最近，随着原颗粒基因(GRN)突变被鉴定为额颞叶变性的重要原因，原颗粒在中枢神经系统中的作用引起了人们的注意。GRN突变与循环中原颗粒蛋白的强烈减少和临床表型差异很大有关：因此，血浆原颗粒蛋白的剂量是快速、廉价地大规模筛查GRN突变携带者的有用工具。目的：建立血浆前颗粒蛋白正常与异常的最佳临界值。方法：在意大利布雷西亚IRCCS S.Giovanni di Dio-Fatebenatelli记忆诊所和意大利米兰Ospedale Maggiore Policlinico阿尔茨海默病中心、IRCCS Maggiore Policlinico和IRCCS Neurologico C.Besta阿尔茨海默病中心分别纳入309例认知健康对照(25~87岁)、72例GRN+零突变携带者(24~86岁)、3例GRN错义突变携带者、342例神经退行性疾病患者和293例轻度认知障碍患者。使用酶联免疫吸附试验试剂盒(Adipogen Inc.，首尔，韩国)测定血浆前颗粒蛋白水平。结果：血浆前颗粒蛋白与年龄、性别和体重指数无关。我们建立了一个新的血浆前颗粒蛋白水平为61.55 ng/ml，以99.6%的特异度和95.8%的灵敏度在记忆诊所的受试者中识别零突变携带者。受影响的GRN零突变携带者和未受影响的GRN零突变携带者在循环原颗粒蛋白方面没有差异(p=0.686)。在原颗粒水平最低的GRN+受试者中观察到显著的疾病预期。结论：我们提出了一个新的血浆前颗粒蛋白水平界值，可用于临床实践。版权所有(C)2011 S.Karger AG，巴塞尔
Background: Recently, attention was drawn to a role for progranulin in the central nervous system with the identification of mutations in the progranulin gene (GRN) as an important cause of frontotemporal lobar degeneration. GRN mutations are associated with a strong reduction of circulating progranulin and widely variable clinical phenotypes: thus, the dosage of plasma progranulin is a useful tool for a quick and inexpensive large-scale screening of carriers of GRN mutations. Objective: To establish the best cutoff threshold for normal versus abnormal levels of plasma progranulin. Methods:309 cognitively healthy controls (25-87 years of age), 72 affected and unaffected GRN+ null mutation carriers (24-86 years of age), 3 affected GRN missense mutation carriers, 342 patients with neurodegenerative diseases and 293 subjects with mild cognitive impairment were enrolled at the Memory Clinic, IRCCS S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy, and at the Alzheimer Unit, Ospedale Maggiore Policlinico and IRCCS Istituto Neurologico C. Besta, Milan, Italy. Plasma progranulin levels were measured using an ELISA kit (AdipoGen Inc., Seoul, Korea). Results: Plasma progranulin did not correlate with age, gender or body mass index. We established a new plasma progranulin protein cutoff level of 61.55 ng/ml that identifies, with a specificity of 99.6% and a sensitivity of 95.8%, null mutation carriers among subjects attending to a memory clinic. Affected and unaffected GRN null mutation carriers did not differ in terms of circulating progranulin protein (p = 0.686). A significant disease anticipation was observed in GRN+ subjects with the lowest progranulin levels. Conclusion: We propose a new plasma progranulin protein cutoff level useful for clinical practice. Copyright (C) 2011 S. Karger AG, Basel