Login Register Cart 0
Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Meta-Analysis

Association of PICALM Gene Polymorphisms with Alzheimer's Disease: Evidence from an Updated Meta-Analysis

Author(s): Fang-Fang Zeng, Jun Liu, Hong He, Xu-Ping Gao, Min-Qi Liao, Xiao-Xuan Yu, Yan-Hua Liu, Sui Zhu and Chun-Xia Jing*

Volume 16, Issue 13, 2019

Page: [1196 - 1205] Pages: 10

DOI: 10.2174/1567205016666190805165607

Price: $65

Abstract

Background: Previous studies have examined the roles of three polymorphisms (rs3851179, rs541458, and rs592297) of the PICALM gene in susceptibility to Alzheimer's disease (AD) with inconclusive findings.

Objective: We performed a meta-analysis to explore whether these three polymorphisms in the PICALM gene were associated with susceptibility to AD.

Methods: Bibliographical searches were conducted in the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. Summary Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were used to assess the strength of association in a random effects model. Potential sources of heterogeneity were identified by subgroup and meta-regression analyses.

Results: Twenty studies (9,017 cases and 15,448 controls) on rs3851179, 12 studies (8,077 cases and 12,022 controls) on rs541458, and 4 studies (2,106 cases and 2,234 controls) on rs592297 were considered eligible for meta-analyses. For both rs3851179 and rs541458, the overall ORs were significant under all genetic models with mild heterogeneity. Compared with G carriers, A carriers of rs3851179 were associated with a decreased risk of AD (OR = 0.88; 95% CI 0.84, 0.91, P for Z-test <0.001, I2 = 0.0%). Compared with T carriers, C carriers of rs541458 were inversely associated with AD risk (OR = 0.86; 95% CI 0.81, 0.92, P for Z-test <0.001, I2 = 39.5%). No association was observed for rs592297. Subgroup and meta-regression analyses indicated that the protective effect of the rs541458 C allele was observed only among Caucasians, not among Asians (P for interaction: 0.021~<0.001).

Conclusion: rs3851179 and rs541458 appear to be associated with decreased AD risk. The null associations for rs592297 with AD risk need further confirmation with a larger number of participants.

Keywords: Alzheimer's disease, single nucleotide polymorphism, PICALM gene, meta-analysis, epidemiology, odds ratio.

« Previous Next »
[1]
Prince M, Wimo A, Guerchet M, Ali G-C, Wu Y-T, Prina M. Alzheimer’s Disease International World Alzheimer Report 2015. The Global Impact of Dementia: An Analysis of Prevelence, Incidence, Cost and Trends; (2015). Available from: https://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf
[2]
Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 3(3): 186-91. (2007)
[http://dx.doi.org/10.1016/j.jalz.2007.04.381] [PMID: 19595937]
[3]
Maurer K, Volk S, Gerbaldo H. Auguste D and Alzheimer’s disease. Lancet 349(9064): 1546-9. (1997)
[http://dx.doi.org/10.1016/S0140-6736(96)10203-8] [PMID: 9167474]
[4]
Scotland PB, Heath JL, Conway AE, Porter NB, Armstrong MB, Walker JA, et al. The PICALM protein plays a key role in iron homeostasis and cell proliferation. PLoS One 7(8)e44252 (2012)
[http://dx.doi.org/10.1371/journal.pone.0044252] [PMID: 22952941]
[5]
Xu W, Tan L, Yu JT. The role of PICALM in Alzheimer’s disease. Mol Neurobiol 52(1): 399-413. (2015)
[http://dx.doi.org/10.1007/s12035-014-8878-3] [PMID: 25186232]
[6]
Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet 41(10): 1088-93. (2009)
[http://dx.doi.org/10.1038/ng.440] [PMID: 19734902]
[7]
Schnetz-Boutaud NC, Hoffman J, Coe JE, Murdock DG, Pericak-Vance MA, Haines JL. Identification and confirmation of an exonic splicing enhancer variation in exon 5 of the Alzheimer disease associated PICALM gene. Ann Hum Genet 76(6): 448-53. (2012)
[http://dx.doi.org/10.1111/j.1469-1809.2012.00727.x] [PMID: 22943764]
[8]
Liu Q, Fang Y. Polymorphisms of PICALM gene in Alzheimer’s disease risk: a meta-analysis. Int J Clin Exp Med 9(6): 10135-46. (2016)
[9]
Wang Z, Lei H, Zheng M, Li Y, Cui Y, Hao F. Meta-analysis of the Association between Alzheimer disease and variants in GAB2, PICALM, and SORL1. Mol Neurobiol 53(9): 6501-10. (2016)
[http://dx.doi.org/10.1007/s12035-015-9546-y] [PMID: 26611835]
[10]
Shankarappa BM, Kota LN, Purushottam M, Nagpal K, Mukherjee O, Viswanath B, et al. Effect of CLU and PICALM polymorphisms on AD risk: a study from south India. Asian J Psychiatr 27: 7-11. (2017)
[http://dx.doi.org/10.1016/j.ajp.2016.12.017] [PMID: 28558900]
[11]
Santos-Rebouças CB, Gonçalves AP, Dos Santos JM, Abdala BB, Motta LB, Laks J, et al. rs3851179 Polymorphism at 5′ to the PICALM gene is associated with Alzheimer and Parkinson diseases in brazilian population. Neuromolecular Med 19(2-3): 293-9. (2017)
[http://dx.doi.org/10.1007/s12017-017-8444-z] [PMID: 28567584]
[12]
Wang HZ, Bi R, Hu QX, et al. Validating GWAS-identified risk loci for Alzheimer’s disease in han chinese populations. Mol Neurobiol 53(1): 379-90. (2016)
[http://dx.doi.org/10.1007/s12035-014-9015-z] [PMID: 25452228]
[13]
Wang LX. The association of PICALM gene re541458 and rs3851179 polymorphisms study for Alzheimer’s Disease in different ethnic groups of Dali district (2015)
[14]
Sen A, Arslan M, Erdal ME, Ay OI, Yilmaz SG, Kurt E, et al. Lack of associations between CLU and PICALM gene polymorphisms and Alzheimer’s Disease in a Turkish population. Ideggyogy Sz 68(3-4): 113-20. (2015)
[PMID: 26434199]
[15]
Jiao B, Liu X, Zhou L, et al. Polygenic analysis of late-onset Alzheimer’s disease from Mainland China. PLoS One 10(12)e0144898 (2015)
[http://dx.doi.org/10.1371/journal.pone.0144898] [PMID: 26680604]
[16]
Hui J. Association analysis of eight gene variations with Alzheimer’s disease susceptibility in northern Chinese populations (2014)
[17]
Omoumi A, Fok A, Greenwood T, Sadovnick AD, Feldman HH, Hsiung GYR. Evaluation of late-onset Alzheimer disease genetic susceptibility risks in a Canadian population. Neurobiol Aging 35(4): 936.e5-936.e12. (2014)
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.09.025] [PMID: 24176626]
[18]
Cohn LD, Becker BJ. How meta-analysis increases statistical power. Psychol Methods 8(3): 243-53. (2003)
[http://dx.doi.org/10.1037/1082-989X.8.3.243] [PMID: 14596489]
[19]
Thakkinstian A, McKay GJ, McEvoy M, Chakravarthy U, Chakrabarti S, Silvestri G, et al. Systematic review and meta-analysis of the association between complement component 3 and age-related macular degeneration: a HuGE review and meta-analysis. Am J Epidemiol 173(12): 1365-79. (2011)
[http://dx.doi.org/10.1093/aje/kwr025] [PMID: 21576320]
[20]
Hedges LV, Pigott TD. The power of statistical tests in meta-analysis. Psychol Methods 6(3): 203-17. (2001)
[http://dx.doi.org/10.1037/1082-989X.6.3.203] [PMID: 11570228]
[21]
Horita N, Kaneko T. Genetic model selection for a case-control study and a meta-analysis. Meta Gene 5: 1-8. (2015)
[http://dx.doi.org/10.1016/j.mgene.2015.04.003] [PMID: 26042205]
[22]
Li M, Li C. Assessing departure from Hardy-Weinberg equilibrium in the presence of disease association. Genet Epidemiol 32(7): 589-99. (2008)
[http://dx.doi.org/10.1002/gepi.20335] [PMID: 18449919]
[23]
Gavaghan DJ, Moore RA, McQuay HJ. An evaluation of homogeneity tests in meta-analyses in pain using simulations of individual patient data. Pain 85(3): 415-24. (2000)
[http://dx.doi.org/10.1016/S0304-3959(99)00302-4] [PMID: 10781914]
[24]
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 327(7414): 557-60. (2003)
[http://dx.doi.org/10.1136/bmj.327.7414.557] [PMID: 12958120]
[25]
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 21(11): 1539-58. (2002)
[http://dx.doi.org/10.1002/sim.1186] [PMID: 12111919]
[26]
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 7(3): 177-88. (1986)
[http://dx.doi.org/10.1016/0197-2456(86)90046-2] [PMID: 3802833]
[27]
Riley RD, Higgins JP, Deeks JJ. Interpretation of random effects meta-analyses. BMJ 342: d549. (2011)
[http://dx.doi.org/10.1136/bmj.d549] [PMID: 21310794]
[28]
Tobias A. Assessing the influence of a single study in the meta-anyalysis estimate. Stata Tech Bull 8(47): 15-7. (1999)
[29]
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109): 629-34. (1997)
[http://dx.doi.org/10.1136/bmj.315.7109.629] [PMID: 9310563]
[30]
Liu G, Zhang L, Feng R, Liao M, Jiang Y, Chen Z, et al. Lack of association between PICALM rs3851179 polymorphism and Alzheimer’s disease in Chinese population and APOEε4-negative subgroup 2013. Neurobiol Aging 34(4): 1310.e9-10 (2013).
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.08.015]
[31]
Li HL. Association of cholesterol metabolism genes with Alzheimer’s disease in Chinese Han population and its possible mechanisms (2012)
[32]
Liu XY. Association analysis of late-onset Alzheimer’s disease and susceptibility genes in Chinese Han population (2014)
[33]
Mao CX, Sun FL, Yu JT, Wu ZC, Zhang Q, Zhang W, et al. Phosphatidylinositol binding clathrin assembly protein gene rs3851179G/A polymorphisms and risk of Alzheimer’s disease. Chin J Clin Neurosci 18(5): 468-73. (2010)
[34]
Liu G, Zhang S, Cai Z, Ma G, Zhang L, Jiang Y, et al. PICALM gene rs3851179 polymorphism contributes to Alzheimer’s disease in an Asian population. Neuromolecular Med 15(2): 384-8. (2013)
[http://dx.doi.org/10.1007/s12017-013-8225-2] [PMID: 23572399]
[35]
Gharesouran J, Rezazadeh M, Khorrami A, Ghojazadeh M, Talebi M. Genetic evidence for the involvement of variants at APOE, BIN1, CR1, and PICALM loci in risk of late-onset Alzheimer’s disease and evaluation for interactions with APOE genotypes. J Mol Neurosci 54(4): 780-6. (2014)
[http://dx.doi.org/10.1007/s12031-014-0377-5] [PMID: 25022885]
[36]
Rezazadeh M, Khorrami A, Yeghaneh T, Talebi M, Kiani SJ, Heshmati Y, et al. Genetic factors affecting late-onset Alzheimer’s disease susceptibility. Neuromolecular Med 18(1): 37-49. (2016)
[http://dx.doi.org/10.1007/s12017-015-8376-4] [PMID: 26553058]
[37]
Belcavello L, Camporez D, Almeida LD, Morelato RL, Batitucci MC, de Paula F. Association of MTHFR and PICALM polymorphisms with Alzheimer’s disease. Mol Biol Rep 42(3): 611-6. (2015)
[http://dx.doi.org/10.1007/s11033-014-3806-1] [PMID: 25359311]
[38]
Klimkowicz-Mrowiec A, Sado M, Dziubek A, Dziedzic T, Pera J, Szczudlik A, et al. Lack of association of CR1, PICALM and CLU gene polymorphisms with Alzheimer disease in a Polish population. Neurol Neurochir Pol 47(2): 157-60. (2013)
[http://dx.doi.org/10.5114/ninp.2013.33825] [PMID: 23650005]
[39]
Ding D. Population-based prevalence survey and genetic epidemiology of cognitive impairment among elderly (2012)
[40]
Ohara T, Ninomiya T, Hirakawa Y, Ashikawa K, Monji A, Kiyohara Y, et al. Association study of susceptibility genes for late-onset Alzheimer’s disease in the Japanese population. Psychiatr Genet 22(6): 290-3. (2012)
[http://dx.doi.org/10.1097/YPG.0b013e3283586215] [PMID: 22935915]
[41]
Chen LH, Kao PY, Fan YH, Ho DT, Chan CS, Yik PY, et al. Polymorphisms of CR1, CLU and PICALM confer susceptibility of Alzheimer's disease in a southern Chinese population. Neurobiol Aging 33(1): 210 e1-7 (2012)
[42]
Yu JT, Song JH, Ma T, Zhang W, Yu NN, Xuan SY, et al. Genetic association of PICALM polymorphisms with Alzheimer’s disease in Han Chinese. J Neurol Sci 300(1-2): 78-80. (2011)
[http://dx.doi.org/10.1016/j.jns.2010.09.027] [PMID: 20951388]
[43]
Piaceri I, Bagnoli S, Lucenteforte E, Mancuso M, Tedde A, Siciliano G, et al. Implication of a genetic variant at PICALM in Alzheimer’s disease patients and centenarians. J Alzheimers Dis 24(3): 409-13. (2011)
[http://dx.doi.org/10.3233/JAD-2011-101791] [PMID: 21297266]
[44]
Li HL, Shi SS, Guo QH, Ni W, Dong Y, Liu Y, et al. PICALM and CR1 variants are not associated with sporadic Alzheimer’s disease in Chinese patients. J Alzheimers Dis 25(1): 111-7. (2011)
[http://dx.doi.org/10.3233/JAD-2011-101917] [PMID: 21358043]
[45]
Seripa D, Panza F, Paroni G, D’Onofrio G, Bisceglia P, Gravina C, et al. Role of CLU, PICALM, and TNK1 genotypes in aging with and without Alzheimer’s disease. Mol Neurobiol 55(5): 4333-44. (2018)
[PMID: 28631188]
[46]
Lambert JC, Zelenika D, Hiltunen M, Chouraki V, Combarros O, Bullido MJ, et al. Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations 2011. Neurobiol Aging 32(4): 756.e11-5. (2011)
[http://dx.doi.org/10.1016/j.neurobiolaging.2010.11.022]
[47]
Jiang T, Yu JT, Tan MS, Wang HF, Wang YL, Zhu XC, et al. Genetic variation in PICALM and Alzheimer’s disease risk in Han Chinese 2014. Neurobiol Aging 35(4): 934.e1-3. (2014)
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.09.014]
[48]
Parikh I, Fardo DW, Estus S. Genetics of PICALM expression and Alzheimer’s disease. PLoS One 9(3)e91242 (2014)
[http://dx.doi.org/10.1371/journal.pone.0091242] [PMID: 24618820]
[49]
Schjeide BM, Schnack C, Lambert JC, Lill CM, Kirchheiner J, Tumani H, et al. The role of clusterin, complement receptor 1, and phosphatidylinositol binding clathrin assembly protein in Alzheimer disease risk and cerebrospinal fluid biomarker levels. Arch Gen Psychiatry 68(2): 207-13. (2011)
[http://dx.doi.org/10.1001/archgenpsychiatry.2010.196] [PMID: 21300948]
[50]
Thomas RS, Henson A, Gerrish A, Jones L, Williams J, Kidd EJ. Decreasing the expression of PICALM reduces endocytosis and the activity of β-secretase: implications for Alzheimer’s disease. BMC Neurosci 17(1): 50. (2016)
[http://dx.doi.org/10.1186/s12868-016-0288-1] [PMID: 27430330]

Rights & Permissions Print Cite
Article Metrics
17
© 2024 Bentham Science Publishers | Privacy Policy