Skip to main content

Advertisement

SpringerLink
Log in

CD33 rs3865444 Polymorphism Contributes to Alzheimer’s Disease Susceptibility in Chinese, European, and North American Populations

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The CD33 rs3865444 polymorphism was first identified to be associated with Alzheimer’s disease (AD) in European population. However, the following studies reported weak or no significant association in Chinese, Japanese, Korean, American, and Canadian populations. We think that these negative results may have been caused by either relatively small sample sizes compared with those used for the previous GWAS in European ancestry or the genetic heterogeneity of the rs3865444 polymorphism in different populations. Here, we reevaluated this association using the relatively large-scale samples from previous 27 studies (N = 86,759; 31,106 cases and 55,653 controls) by searching the PubMed, AlzGene, and Google Scholar databases. We identified significant heterogeneity and observed no significant association between the rs3865444 polymorphism and AD in pooled populations (P = 0.264, odds ratio (OR) = 0.97, 95 % confidence interval (CI) 0.93–1.02). In subgroup analysis, we identified significant heterogeneity only in East Asian population and observed no significant association between the rs3865444 polymorphism and AD. We further identified significant heterogeneity and observed significant association between the rs3865444 polymorphism and AD in Chinese population. We identified no significant heterogeneity and significant association in North American and European populations. Collectively, our analysis shows that the CD33 rs3865444 polymorphism is associated with AD susceptibility in Chinese, European, and North American populations. We believe that our findings will be very useful for future genetic studies on AD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Liu G, Jiang Y, Wang P, Feng R, Jiang N, Chen X, Song H, Chen Z (2012) Cell adhesion molecules contribute to Alzheimer’s disease: multiple pathway analyses of two genome-wide association studies. J Neurochem 120:190–198

    Article  CAS  PubMed  Google Scholar 

  2. Liu G, Yao L, Liu J, Jiang Y, Ma G, Chen Z, Zhao B, Li K (2014) Cardiovascular disease contributes to Alzheimer’s disease: evidence from large-scale genome-wide association studies. Neurobiol Aging 35:786–792

    Article  PubMed  Google Scholar 

  3. Liu G, Wang H, Liu J, Li J, Li H, Ma G, Jiang Y, Chen Z, Zhao B, Li K (2014) The clu gene rs11136000 variant is significantly associated with Alzheimer’s disease in Caucasian and Asian populations. Neuromol Med 16:52–60

    Article  Google Scholar 

  4. Naj AC, Jun G, Beecham GW, Wang LS, Vardarajan BN, Buros J, Gallins PJ, Buxbaum JD, Jarvik GP, Crane PK, Larson EB, Bird TD, Boeve BF, Graff-Radford NR, De Jager PL, Evans D, Schneider JA, Carrasquillo MM, Ertekin-Taner N, Younkin SG, Cruchaga C, Kauwe JS, Nowotny P, Kramer P, Hardy J, Huentelman MJ, Myers AJ, Barmada MM, Demirci FY, Baldwin CT, Green RC, Rogaeva E, St George-Hyslop P, Arnold SE, Barber R, Beach T, Bigio EH, Bowen JD, Boxer A, Burke JR, Cairns NJ, Carlson CS, Carney RM, Carroll SL, Chui HC, Clark DG, Corneveaux J, Cotman CW, Cummings JL, DeCarli C, DeKosky ST, Diaz-Arrastia R, Dick M, Dickson DW, Ellis WG, Faber KM, Fallon KB, Farlow MR, Ferris S, Frosch MP, Galasko DR, Ganguli M, Gearing M, Geschwind DH, Ghetti B, Gilbert JR, Gilman S, Giordani B, Glass JD, Growdon JH, Hamilton RL, Harrell LE, Head E, Honig LS, Hulette CM, Hyman BT, Jicha GA, Jin LW, Johnson N, Karlawish J, Karydas A, Kaye JA, Kim R, Koo EH, Kowall NW, Lah JJ, Levey AI, Lieberman AP, Lopez OL, Mack WJ, Marson DC, Martiniuk F, Mash DC, Masliah E, McCormick WC, McCurry SM, McDavid AN, McKee AC, Mesulam M, Miller BL, Miller CA, Miller JW, Parisi JE, Perl DP, Peskind E, Petersen RC, Poon WW, Quinn JF, Rajbhandary RA, Raskind M, Reisberg B, Ringman JM, Roberson ED, Rosenberg RN, Sano M, Schneider LS, Seeley W, Shelanski ML, Slifer MA, Smith CD, Sonnen JA, Spina S, Stern RA, Tanzi RE, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Williamson J, Woltjer RL, Cantwell LB, Dombroski BA, Beekly D, Lunetta KL, Martin ER, Kamboh MI, Saykin AJ, Reiman EM, Bennett DA, Morris JC, Montine TJ, Goate AM, Blacker D, Tsuang DW, Hakonarson H, Kukull WA, Foroud TM, Haines JL, Mayeux R, Pericak-Vance MA, Farrer LA, Schellenberg GD (2011) Common variants at ms4a4/ms4a6e, cd2ap, cd33 and epha1 are associated with late-onset Alzheimer’s disease. Nat Genet 43:436–441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM, Abraham R, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Jones N, Stretton A, Thomas C, Richards A, Ivanov D, Widdowson C, Chapman J, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, Mann D, Smith AD, Beaumont H, Warden D, Wilcock G, Love S, Kehoe PG, Hooper NM, Vardy ER, Hardy J, Mead S, Fox NC, Rossor M, Collinge J, Maier W, Jessen F, Ruther E, Schurmann B, Heun R, Kolsch H, van den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Frolich L, Hampel H, Gallacher J, Hull M, Rujescu D, Giegling I, Goate AM, Kauwe JS, Cruchaga C, Nowotny P, Morris JC, Mayo K, Sleegers K, Bettens K, Engelborghs S, De Deyn PP, Van Broeckhoven C, Livingston G, Bass NJ, Gurling H, McQuillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Tsolaki M, Singleton AB, Guerreiro R, Muhleisen TW, Nothen MM, Moebus S, Jockel KH, Klopp N, Wichmann HE, Pankratz VS, Sando SB, Aasly JO, Barcikowska M, Wszolek ZK, Dickson DW, Graff-Radford NR, Petersen RC, van Duijn CM, Breteler MM, Ikram MA, DeStefano AL, Fitzpatrick AL, Lopez O, Launer LJ, Seshadri S, Berr C, Campion D, Epelbaum J, Dartigues JF, Tzourio C, Alperovitch A, Lathrop M, Feulner TM, Friedrich P, Riehle C, Krawczak M, Schreiber S, Mayhaus M, Nicolhaus S, Wagenpfeil S, Steinberg S, Stefansson H, Stefansson K, Snaedal J, Bjornsson S, Jonsson PV, Chouraki V, Genier-Boley B, Hiltunen M, Soininen H, Combarros O, Zelenika D, Delepine M, Bullido MJ, Pasquier F, Mateo I, Frank-Garcia A, Porcellini E, Hanon O, Coto E, Alvarez V, Bosco P, Siciliano G, Mancuso M, Panza F, Solfrizzi V, Nacmias B, Sorbi S, Bossu P, Piccardi P, Arosio B, Annoni G, Seripa D, Pilotto A, Scarpini E, Galimberti D, Brice A, Hannequin D, Licastro F, Jones L, Holmans PA, Jonsson T, Riemenschneider M, Morgan K, Younkin SG, Owen MJ, O’Donovan M, Amouyel P, Williams J (2011) Common variants at abca7, ms4a6a/ms4a4e, epha1, cd33 and cd2ap are associated with Alzheimer’s disease. Nat Genet 43:429–435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, Jun G, Destefano AL, Bis JC, Beecham GW, Grenier-Boley B, Russo G, Thornton-Wells TA, Jones N, Smith AV, Chouraki V, Thomas C, Ikram MA, Zelenika D, Vardarajan BN, Kamatani Y, Lin CF, Gerrish A, Schmidt H, Kunkle B, Dunstan ML, Ruiz A, Bihoreau MT, Choi SH, Reitz C, Pasquier F, Hollingworth P, Ramirez A, Hanon O, Fitzpatrick AL, Buxbaum JD, Campion D, Crane PK, Baldwin C, Becker T, Gudnason V, Cruchaga C, Craig D, Amin N, Berr C, Lopez OL, De Jager PL, Deramecourt V, Johnston JA, Evans D, Lovestone S, Letenneur L, Moron FJ, Rubinsztein DC, Eiriksdottir G, Sleegers K, Goate AM, Fievet N, Huentelman MJ, Gill M, Brown K, Kamboh MI, Keller L, Barberger-Gateau P, McGuinness B, Larson EB, Green R, Myers AJ, Dufouil C, Todd S, Wallon D, Love S, Rogaeva E, Gallacher J, St George-Hyslop P, Clarimon J, Lleo A, Bayer A, Tsuang DW, Yu L, Tsolaki M, Bossu P, Spalletta G, Proitsi P, Collinge J, Sorbi S, Sanchez-Garcia F, Fox NC, Hardy J, Naranjo MC, Bosco P, Clarke R, Brayne C, Galimberti D, Mancuso M, Matthews F, Moebus S, Mecocci P, Del Zompo M, Maier W, Hampel H, Pilotto A, Bullido M, Panza F, Caffarra P, Nacmias B, Gilbert JR, Mayhaus M, Lannfelt L, Hakonarson H, Pichler S, Carrasquillo MM, Ingelsson M, Beekly D, Alvarez V, Zou F, Valladares O, Younkin SG, Coto E, Hamilton-Nelson KL, Gu W, Razquin C, Pastor P, Mateo I, Owen MJ, Faber KM, Jonsson PV, Combarros O, O’Donovan MC, Cantwell LB, Soininen H, Blacker D, Mead S, Mosley TH Jr, Bennett DA, Harris TB, Fratiglioni L, Holmes C, de Bruijn RF, Passmore P, Montine TJ, Bettens K, Rotter JI, Brice A, Morgan K, Foroud TM, Kukull WA, Hannequin D, Powell JF, Nalls MA, Ritchie K, Lunetta KL, Kauwe JS, Boerwinkle E, Riemenschneider M, Boada M, Hiltunen M, Martin ER, Schmidt R, Rujescu D, Wang LS, Dartigues JF, Mayeux R, Tzourio C, Hofman A, Nothen MM, Graff C, Psaty BM, Jones L, Haines JL, Holmans PA, Lathrop M, Pericak-Vance MA, Launer LJ, Farrer LA, van Duijn CM, Van Broeckhoven C, Moskvina V, Seshadri S, Williams J, Schellenberg GD, Amouyel P (2013) Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet 45:1452–1458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Deng YL, Liu LH, Wang Y, Tang HD, Ren RJ, Xu W, Ma JF, Wang LL, Zhuang JP, Wang G, Chen SD (2012) The prevalence of cd33 and ms4a6a variant in Chinese Han population with Alzheimer’s disease. Hum Genet 131:1245–1249

    Article  CAS  PubMed  Google Scholar 

  8. Tan L, Yu JT, Zhang W, Wu ZC, Zhang Q, Liu QY, Wang W, Wang HF, Ma XY, Cui WZ (2013) Association of GWAS-linked loci with late-onset Alzheimer’s disease in a northern Han Chinese population. Alzheimers Dement 9:546–553

    Article  PubMed  Google Scholar 

  9. Miyashita A, Koike A, Jun G, Wang LS, Takahashi S, Matsubara E, Kawarabayashi T, Shoji M, Tomita N, Arai H, Asada T, Harigaya Y, Ikeda M, Amari M, Hanyu H, Higuchi S, Ikeuchi T, Nishizawa M, Suga M, Kawase Y, Akatsu H, Kosaka K, Yamamoto T, Imagawa M, Hamaguchi T, Yamada M, Moriaha T, Takeda M, Takao T, Nakata K, Fujisawa Y, Sasaki K, Watanabe K, Nakashima K, Urakami K, Ooya T, Takahashi M, Yuzuriha T, Serikawa K, Yoshimoto S, Nakagawa R, Kim JW, Ki CS, Won HH, Na DL, Seo SW, Mook-Jung I, St George-Hyslop P, Mayeux R, Haines JL, Pericak-Vance MA, Yoshida M, Nishida N, Tokunaga K, Yamamoto K, Tsuji S, Kanazawa I, Ihara Y, Schellenberg GD, Farrer LA, Kuwano R (2013) Sorl1 is genetically associated with late-onset Alzheimer’s disease in Japanese, Koreans and Caucasians. PLoS One 8:e58618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chung SJ, Lee JH, Kim SY, You S, Kim MJ, Lee JY, Koh J (2013) Association of GWAS top hits with late-onset Alzheimer disease in Korean population. Alzheimer Dis Assoc Disord 27:250–257

    Article  CAS  PubMed  Google Scholar 

  11. Omoumi A, Fok A, Greenwood T, Sadovnick AD, Feldman HH, Hsiung GY (2014) Evaluation of late-onset Alzheimer disease genetic susceptibility risks in a Canadian population. Neurobiol Aging 35:936, e935-912

    Article  PubMed  Google Scholar 

  12. Logue MW, Schu M, Vardarajan BN, Buros J, Green RC, Go RC, Griffith P, Obisesan TO, Shatz R, Borenstein A, Cupples LA, Lunetta KL, Fallin MD, Baldwin CT, Farrer LA (2011) A comprehensive genetic association study of Alzheimer disease in African Americans. Arch Neurol 68:1569–1579

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lewis CM, Knight J (2012) Introduction to genetic association studies. Cold Spring Harb Protoc 2012:297–306

    Article  PubMed  Google Scholar 

  14. Liu G, Zhang S, Cai Z, Ma G, Zhang L, Jiang Y, Feng R, Liao M, Chen Z, Zhao B, Li K (2013) Picalm gene rs3851179 polymorphism contributes to Alzheimer’s disease in an Asian population. Neuromol Med 15:384–388

    Article  CAS  Google Scholar 

  15. Jiang Y, Zhang R, Zheng J, Liu P, Tang G, Lv H, Zhang L, Shang Z, Zhan Y, Lv W, Shi M (2012) Meta-analysis of 125 rheumatoid arthritis-related single nucleotide polymorphisms studied in the past two decades. PLoS One 7:e51571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Carrasquillo MM, Belbin O, Hunter TA, Ma L, Bisceglio GD, Zou F, Crook JE, Pankratz VS, Sando SB, Aasly JO, Barcikowska M, Wszolek ZK, Dickson DW, Graff-Radford NR, Petersen RC, Passmore P, Morgan K, Younkin SG (2011) Replication of epha1 and cd33 associations with late-onset Alzheimer’s disease: a multi-centre case–control study. Mol Neurodegener 6:54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bradshaw EM, Chibnik LB, Keenan BT, Ottoboni L, Raj T, Tang A, Rosenkrantz LL, Imboywa S, Lee M, Von Korff A, Morris MC, Evans DA, Johnson K, Sperling RA, Schneider JA, Bennett DA, De Jager PL (2013) Cd33 Alzheimer’s disease locus: altered monocyte function and amyloid biology. Nat Neurosci 16:848–850

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Griciuc A, Serrano-Pozo A, Parrado AR, Lesinski AN, Asselin CN, Mullin K, Hooli B, Choi SH, Hyman BT, Tanzi RE (2013) Alzheimer’s disease risk gene cd33 inhibits microglial uptake of amyloid beta. Neuron 78:631–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Raj T, Ryan KJ, Replogle JM, Chibnik LB, Rosenkrantz L, Tang A, Rothamel K, Stranger BE, Bennett DA, Evans DA, De Jager PL, Bradshaw EM (2014) Cd33: increased inclusion of exon 2 implicates the ig v-set domain in Alzheimer’s disease susceptibility. Hum Mol Genet 23:2729–2736

    Article  CAS  PubMed  Google Scholar 

  20. Liu G, Zhang S, Cai Z, Li Y, Cui L, Ma G, Jiang Y, Zhang L, Feng R, Liao M, Chen Z, Zhao B, Li K (2013) Bin1 gene rs744373 polymorphism contributes to Alzheimer’s disease in East Asian population. Neurosci Lett 544:47–51

    Article  CAS  PubMed  Google Scholar 

  21. Liu G, Zhang L, Feng R, Liao M, Jiang Y, Chen Z, Zhao B, Li K (2013) Lack of association between picalm rs3851179 polymorphism and Alzheimer’s disease in Chinese population and apoeepsilon4-negative subgroup. Neurobiol Aging 34:1310, e1319-1310

    CAS  PubMed  Google Scholar 

  22. Liu G, Li F, Zhang S, Jiang Y, Ma G, Shang H, Liu J, Feng R, Zhang L, Liao M, Zhao B, Li K (2014) Analyzing large-scale samples confirms the association between the abca7 rs3764650 polymorphism and Alzheimer’s disease susceptibility. Mol Neurobiol

  23. Shen N, Chen B, Jiang Y, Feng R, Liao M, Zhang L, Li F, Ma G, Chen Z, Zhao B, Li K, Liu G (2014) An updated analysis with 85,939 samples confirms the association between cr1 rs6656401 polymorphism and Alzheimer’s disease. Mol Neurobiol

  24. Zhang S, Zhang D, Jiang Y, Wu L, Shang H, Liu J, Feng R, Liao M, Zhang L, Liu Y, Liu G, Li K (2014) Clu rs2279590 polymorphism contributes to Alzheimer’s disease susceptibility in Caucasian and Asian populations. J Neural Transm

  25. Gogele M, Minelli C, Thakkinstian A, Yurkiewich A, Pattaro C, Pramstaller PP, Little J, Attia J, Thompson JR (2012) Methods for meta-analyses of genome-wide association studies: critical assessment of empirical evidence. Am J Epidemiol 175:739–749

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by funding from the National Nature Science Foundation of China (grant numbers 81300945, 31200934, 31301938, 81471294, 31171219, 81271213, 81271214) and the Natural Science Foundation of Zhejiang Province, China (LY12H04006 to Li XW).

Conflict of Interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

    Xingwang Li

  2. Department of Physiology, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, China

    Ning Shen

  3. Department of Neurology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China

    Shuyan Zhang

  4. Department of Neurology, The First Hospital of Harbin, Harbin, China

    Jiafeng Liu

  5. Academy of Fundamental and Interdisciplinary Sciences, Harbin Institute of Technology, Harbin, Heilongjiang, China

    Qinghua Jiang

  6. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China

    Mingzhi Liao & Yongshuai Jiang

  7. Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China

    Rennan Feng

  8. Department of Statistics, Rice University, Houston, TX, USA

    Liangcai Zhang

  9. Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China

    Guangyu Wang

  10. Institute of Neurology, Guangdong Medical College, Zhanjiang, 524001, China

    Guoda Ma, Haihong Zhou, Bin Zhao & Keshen Li

  11. Department of Human Genetics, University of California at Los Angeles, Los Angeles, CA, USA

    Zugen Chen

  12. Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Beijing, China

    Guiyou Liu

  13. Key Laboratory of Aging-Related Cardio-Cerebral Diseases of Guangdong Province, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China

    Bin Zhao

  14. Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Xiqi Dao 32, Tianjin Airport Economic Area, Tianjin, 300308, China

    Guiyou Liu

Authors
  1. Xingwang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ning Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shuyan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiafeng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qinghua Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mingzhi Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rennan Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Liangcai Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Guangyu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Guoda Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Haihong Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Zugen Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yongshuai Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Bin Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Keshen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Guiyou Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yongshuai Jiang, Bin Zhao, Keshen Li or Guiyou Liu.

Additional information

Xingwang Li, Ning Shen, and Shuyan Zhang contributed equally to this work.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 391 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Shen, N., Zhang, S. et al. CD33 rs3865444 Polymorphism Contributes to Alzheimer’s Disease Susceptibility in Chinese, European, and North American Populations. Mol Neurobiol 52, 414–421 (2015). https://doi.org/10.1007/s12035-014-8880-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-014-8880-9

Keywords

Search

Navigation