Abstract
The rs3851179 which located at upstream of PICALM was reported to be associated with Alzheimer’s disease (AD); however, the relationship is still undefined. To gain a more precise understanding of the association, we conducted a meta-analysis: a comprehensive survey of 16 case-control studies that evaluated the role of rs3851179 gene variants in AD patients. The overall analysis revealed a significant association between the polymorphism and AD in the allelic, homozygote, heterozygote, dominant, and recessive models (p < 0.05). When stratified by ethnicity, a significant association was observed between AD development in Caucasian populations and the five-genetic models; Asian populations, however, featured a significant association in only the allelic, homozygote, and recessive models. We did not observe any influence of APOE ε4 carrier status on the incidence of AD and rs3851179 (p > 0.05). Our meta-analysis thus suggested that the PICALM rs3851179 polymorphism was associated with AD; the APOE ε4 status did not influence the relationship. Nevertheless, considering the limitations of our meta-analysis, further large-scale studies should be conducted to gain a more comprehensive understanding.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alzheimer’s Association (2015) 2015 Alzheimer's disease facts and figures. Alzheimers Dement 11:332–384
Bettens K, Sleegers K, Van Broeckhoven C (2013) Genetic insights in Alzheimer's disease. Lancet Neurol 12:92–104. https://doi.org/10.1016/S1474-4422(12)70259-4
Bushlin I, Petralia RS, Wu F, Harel A, Mughal MR, Mattson MP et al (2008) Clathrin assembly protein AP180 and CALM differentially control axogenesis and dendrite outgrowth in embryonic hippocampal neurons. J Neurosci 28:10257–10271. https://doi.org/10.1523/JNEUROSCI.2471-08.2008
Carrasquillo MM, Belbin O, Hunter TA, Ma L, Bisceglio GD, Zou F et al (2010) Replication of CLU, CR1, and PICALM associations with alzheimer disease. Arch Neurol 67:961–964. https://doi.org/10.1001/archneurol.2010.147
Chen LH, Kao PY, Fan YH, Ho DT, Chan CS, Yik PY et al (2012) Polymorphisms of CR1, CLU and PICALM confer susceptibility of Alzheimer's disease in a southern Chinese population. Neurobiol Aging 33:210–211. https://doi.org/10.1016/j.neurobiolaging.2011.09.016
Ding D (2012) Population-based prevalence survey and genetic epidemiology of cognitive impairment among elderly. Fudan University
Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML et al (2009) Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet 41:1088–1093. https://doi.org/10.1038/ng.440
Hui J (2014) Association analysis of eight gen variations with alzheimer's disease susceptibility in Northen Chinese population. Ningxia Medical University
Kanatsu K, Hori Y, Takatori S, Watanabe T, Iwatsubo T, Tomita T (2016) Partial loss of CALM function reduces Abeta42 production and amyloid deposition in vivo. Hum Mol Genet 25:3988–3997. https://doi.org/10.1093/hmg/ddw239
Klimkowicz-Mrowiec A, Sado M, Dziubek A, Dziedzic T, Pera J, Szczudlik A et al (2013) Lack of association of CR1, PICALM and CLU gene polymorphisms with Alzheimer disease in a Polish population. Neurol Neurochir Pol 47:157–160
Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M et al (2009) Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat Genet 41:1094–1099. https://doi.org/10.1038/ng.439
Li HL, Shi SS, Guo QH, Ni W, Dong Y, Liu Y et al (2011) PICALM and CR1 variants are not associated with sporadic Alzheimer's disease in Chinese patients. J Alzheimers Dis 25:111–117. https://doi.org/10.3233/JAD-2011-101917
Liu XY (2014) The Association analysis of late-onset Alzheimer's disease and susceptibility genes in Chinese Han population. Central South University
Liu G, Zhang S, Cai Z, Ma G, Zhang L, Jiang Y et al (2013) PICALM gene rs3851179 polymorphism contributes to Alzheimer's disease in an Asian population. NeuroMolecular Med 15:384–388. https://doi.org/10.1007/s12017-013-8225-2
Liu G, Xu Y, Jiang Y, Zhang L, Feng R, Jiang Q (2017) PICALM rs3851179 variant confers susceptibility to Alzheimer's disease in Chinese population. Mol Neurobiol 54:3131–3136. https://doi.org/10.1007/s12035-016-9886-2
Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC et al (2010) Decreased clearance of CNS beta-amyloid in Alzheimer's disease. Science 330:1774. https://doi.org/10.1126/science.1197623
Mengel-From J, Thinggaard M, Lindahl-Jacobsen R, McGue M, Christensen K, Christiansen L (2013) CLU genetic variants and cognitive decline among elderly and oldest old. PLoS One 8:e79105. https://doi.org/10.1371/journal.pone.0079105
Michaelson DM (2014) APOE epsilon4: the most prevalent yet understudied risk factor for Alzheimer's disease. Alzheimers Dement 10:861–868. https://doi.org/10.1016/j.jalz.2014.06.015
Ohara T, Ninomiya T, Hirakawa Y, Ashikawa K, Monji A, Kiyohara Y et al (2012) Association study of susceptibility genes for late-onset Alzheimer's disease in the Japanese population. Psychiatr Genet 22:290–293. https://doi.org/10.1097/YPG.0b013e3283586215
Piaceri I, Bagnoli S, Lucenteforte E, Mancuso M, Tedde A, Siciliano G et al (2011) Implication of a genetic variant at PICALM in Alzheimer's disease patients and centenarians. J Alzheimers Dis 24:409–413. https://doi.org/10.3233/JAD-2011-101791
Santos-Reboucas CB, Goncalves AP, Dos SJ, Abdala BB, Motta LB, Laks J et al (2017) rs3851179 polymorphism at 5′ to the PICALM gene is associated with Alzheimer and Parkinson diseases in Brazilian population. NeuroMolecular Med. https://doi.org/10.1007/s12017-017-8444-z
Seshadri S, Fitzpatrick AL, Ikram MA, DeStefano AL, Gudnason V, Boada M et al (2010) Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA 303:1832–1840. https://doi.org/10.1001/jama.2010.574
Shankarappa BM, Kota LN, Purushottam M, Nagpal K, Mukherjee O, Viswanath B et al (2017) Effect of CLU and PICALM polymorphisms on AD risk: a study from South India. Asian J Psychiatr 27:7–11. https://doi.org/10.1016/j.ajp.2016.12.017
Thomas RS, Henson A, Gerrish A, Jones L, Williams J, Kidd EJ (2016) Decreasing the expression of PICALM reduces endocytosis and the activity of beta-secretase: implications for Alzheimer's disease. BMC Neurosci 17:50. https://doi.org/10.1186/s12868-016-0288-1
Tosto G, Bird TD, Bennett DA, Boeve BF, Brickman AM, Cruchaga C et al (2016) The role of cardiovascular risk factors and stroke in familial Alzheimer disease. JAMA Neurol 73:1231–1237. https://doi.org/10.1001/jamaneurol.2016.2539
Wang HZ, Bi R, Hu QX, Xiang Q, Zhang C, Zhang DF et al (2016) Validating GWAS-identified risk loci for Alzheimer's disease in Han Chinese populations. Mol Neurobiol 53:379–390. https://doi.org/10.1007/s12035-014-9015-z
Wang Y, Liu S, Wang J, Zhang J, Hua Y, Li H et al (2017) Association between LRP1 C766T polymorphism and Alzheimer's disease susceptibility: a meta-analysis. Sci Rep 7:8435. https://doi.org/10.1038/s41598-017-08335-w
Yu JT, Song JH, Ma T, Zhang W, Yu NN, Xuan SY et al (2011) Genetic association of PICALM polymorphisms with Alzheimer's disease in Han Chinese. J Neurol Sci 300:78–80. https://doi.org/10.1016/j.jns.2010.09.027
Zhang S, Wang XB, Han YD, Wang C, Zhou Y, Zheng F (2017) Certain polymorphisms in SP110 gene confer susceptibility to tuberculosis: a comprehensive review and updated meta-analysis. Yonsei Med J 58:165–173. https://doi.org/10.3349/ymj.2017.58.1.165
Zhao Z, Sagare AP, Ma Q, Halliday MR, Kong P, Kisler K et al (2015) Central role for PICALM in amyloid-beta blood-brain barrier transcytosis and clearance. Nat Neurosci 18:978–987. https://doi.org/10.1038/nn.4025
Zhu B, Wang RM, Wang JT, Chen RL, Zheng YF, Zhang L et al (2017) Correlation of rs9331888 polymorphism with Alzheimer's disease among Caucasian and Chinese populations: a meta-analysis and systematic review. Metab Brain Dis 32:981–989. https://doi.org/10.1007/s11011-017-9957-8
Acknowledgments
This work was supported by Beijing Municipal Administration of Hospitals’ Youth Programme (grant number: QML20170703), China Postdoctoral Science Foundation (No.2017M620700), Beijing Natural Science Foundation (grant number:7164256), The National Key Research and Development Program of China (grant number: 2016YFC1306300) and The Key Project of Natural Science Foundation of Beijing, China (grant number:4161004).
Author information
Authors and Affiliations
Contributions
BZ. and ZGZ designed this study and had full access to all of the data in the study; LXL and SYA acquisition of data, LZ, YT and SSG analysis and interpretation of data. WZ Critical revision of the manuscript.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Rights and permissions
About this article
Cite this article
Zhu, B., Li, LX., Zhang, L. et al. Correlation of PICALM polymorphism rs3851179 with Alzheimer’s disease among Caucasian and Chinese populations: a meta-analysis and systematic review. Metab Brain Dis 33, 1849–1857 (2018). https://doi.org/10.1007/s11011-018-0291-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-018-0291-6