title: PGRN Is Associated with Late-Onset Alzheimer's Disease: a Case-Control Replication Study and Meta-analysis.
abstract: Progranulin (PGRN) plays an important role in Alzheimer's disease (AD) through participating in altering neurite outgrowth and neuronal survival. Previous studies identified that rs5848 in the 3'-untranslated region (3'-UTR) of the PGRN gene (GRN) is strongly associated with AD in Caucasians. In order to assess the involvement of the GRN polymorphism in the risk of late-onset AD (LOAD), we analyzed the genotype and allele distributions of rs5848 in 2350 Han Chinese subjects (AD, 992; control, 1358). The minor T allele of rs5848 was significantly associated with an increased risk of LOAD (P = 0.005, odds ratio (OR) = 1.197, 95 % confidence interval (CI) = 1.057-1.355). Moreover, the association was further validated in the multivariate logistic regression analysis (dominant model: OR = 1.195, P = 0.038, recessive model: OR = 1.386, P = 0.025; additive model: OR = 1.187, P = 0.009). Interestingly, we observed that the interaction between apolipoprotein E (APOE) and rs5848 significantly altered the risk for AD. The rs5848 polymorphism was only significantly associated with LOAD in APOE ε4 allele carriers. Then we included five studies (including the present study) and conducted a meta-analysis which consisted of 3236 cases (male, 1152; female, 2084) and 3405 (male, 1436; female, 1969) controls. The result of the meta-analysis supported T allele of rs5848 within GRN as a risk factor for AD. In conclusion, our results demonstrated that rs5848 polymorphism within GRN was associated with LOAD.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Taishan Medical University, Qingdao, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Xu
authors.affiliation: College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.affiliation: Department of Emergency, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Geriatric, Qingdao Mental Health Center, Qingdao, 266034, China.
authors.forename: Zhan-Jie
authors.initials: ZJ
authors.lastname: Zheng
authors.affiliation: Department of Geriatric, Qingdao Mental Health Center, Qingdao, 266034, China.
authors.forename: Ling-Li
authors.initials: LL
authors.lastname: Kong
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China.
authors.forename: Zi-Xuan
authors.initials: ZX
authors.lastname: Wang
authors.affiliation: Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Taishan Medical University, Qingdao, China. dr.tanlan@163.com.|College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266000, China. dr.tanlan@163.com.|Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China. dr.tanlan@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China. yu-jintai@163.com.|Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA. yu-jintai@163.com.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004261:DNA Replication / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D000077153:Progranulins
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
keywords: Alzheimer’s disease; Meta-analysis; Polymorphism; Progranulin; rs5848
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