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PGRN Is Associated with Late-Onset Alzheimer’s Disease: a Case–Control Replication Study and Meta-analysis

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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.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81471309, 81371406, 81571245, and 81501103), the Shandong Provincial Outstanding Medical Academic Professional Program, Qingdao Key Health Discipline Development Fund, Qingdao Outstanding Health Professional Development Fund, and Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders.

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Authors and Affiliations

  1. Department of Neurology, Qingdao Municipal Hospital, Taishan Medical University, Qingdao, China

    Hui-Min Xu & Lan Tan

  2. College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266000, China

    Lin Tan & Lan Tan

  3. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China

    Yu Wan, Meng-Shan Tan, Zi-Xuan Wang, Lan Tan & Jin-Tai Yu

  4. Department of Emergency, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China

    Wei Zhang

  5. Department of Geriatric, Qingdao Mental Health Center, Qingdao, 266034, China

    Zhan-Jie Zheng & Ling-Li Kong

  6. Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China

    Teng Jiang

  7. Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA

    Jin-Tai Yu

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  1. Hui-Min Xu
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  10. Lan Tan
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Correspondence to Lan Tan or Jin-Tai Yu.

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Written informed consent was obtained from each participant or their guardian, and our study was approved by the Ethical Committee of Qingdao Municipal Hospital (2009-05-06-003).

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The authors declare that they have no competing interests.

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Hui-Min Xu and Lin Tan should be regarded as co-first authors.

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Xu, HM., Tan, L., Wan, Y. et al. PGRN Is Associated with Late-Onset Alzheimer’s Disease: a Case–Control Replication Study and Meta-analysis. Mol Neurobiol 54, 1187–1195 (2017). https://doi.org/10.1007/s12035-016-9698-4

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