Metabolic Brain Disease

, Volume 33, Issue 6, pp 1849–1857 | Cite as

Correlation of PICALM polymorphism rs3851179 with Alzheimer’s disease among Caucasian and Chinese populations: a meta-analysis and systematic review

  • Bin Zhu
  • Li-Xia Li
  • Lei Zhang
  • Shu Yang
  • Yue Tian
  • Shan-Shan Guo
  • Wei Zhang
  • Zhi-Gang Zhao
Original Article


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.


PICALM Alzheimer’s disease rs3851179 APOE ε4 Polymorphism 



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’s 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.

Compliance with ethical standards

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.


  1. Alzheimer’s Association (2015) 2015 Alzheimer's disease facts and figures. Alzheimers Dement 11:332–384CrossRefGoogle Scholar
  2. Bettens K, Sleegers K, Van Broeckhoven C (2013) Genetic insights in Alzheimer's disease. Lancet Neurol 12:92–104. CrossRefPubMedGoogle Scholar
  3. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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. CrossRefPubMedGoogle Scholar
  6. Ding D (2012) Population-based prevalence survey and genetic epidemiology of cognitive impairment among elderly. Fudan UniversityGoogle Scholar
  7. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  8. Hui J (2014) Association analysis of eight gen variations with alzheimer's disease susceptibility in Northen Chinese population. Ningxia Medical UniversityGoogle Scholar
  9. 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. CrossRefPubMedGoogle Scholar
  10. 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 47:157–160PubMedGoogle Scholar
  11. 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. CrossRefPubMedGoogle Scholar
  12. 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. CrossRefPubMedGoogle Scholar
  13. Liu XY (2014) The Association analysis of late-onset Alzheimer's disease and susceptibility genes in Chinese Han population. Central South UniversityGoogle Scholar
  14. 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. CrossRefPubMedGoogle Scholar
  15. 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. CrossRefPubMedGoogle Scholar
  16. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  18. Michaelson DM (2014) APOE epsilon4: the most prevalent yet understudied risk factor for Alzheimer's disease. Alzheimers Dement 10:861–868. CrossRefPubMedGoogle Scholar
  19. 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. CrossRefPubMedGoogle Scholar
  20. 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. CrossRefPubMedGoogle Scholar
  21. 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. CrossRefGoogle Scholar
  22. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 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. CrossRefPubMedGoogle Scholar
  24. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 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. CrossRefPubMedGoogle Scholar
  27. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 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. CrossRefPubMedGoogle Scholar
  29. 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. CrossRefPubMedGoogle Scholar
  30. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 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. CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmacy, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina
  2. 2.Department of Geriatrics, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina
  3. 3.Department of Pharmacy, Beijing Shijitan HospitalCapital Medical UniversityBeijingChina

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