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Journal of Integrative Neuroscience  2018, Vol. 17 Issue (4): 313-321    DOI: 10.31083/j.jin.2018.04.0408
Research article Previous articles | Next articles
Associations between CD33 rs3865444 and ABCA7 rs3764650 polymorphisms and susceptibility to Alzheimer's disease
Jing Wang1, Xiangyi Kong2, Lele Cong1, Zhongxin Xu1, Jianshi Du2, Xianling Cong3, Hongyan Sun3, Yanan Xu1, Qing Zhao1, *()
1 Department of Neurology, China-Japan Union Hospital of Jilin University, Chang Chun, 130033, Jilin Province, China
2 Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin Province, China
3 Department of Biobank, China-Japan Unoin Hospital, Jilin University, Changchun, 130033, Jilin Province, China
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Abstract  

Several studies have evaluated the association of Siglec-3(CD33) rs3865444 polymorphism and ATP-binding cassette transporter A7(ABCA7) rs3764650 polymorphism with susceptibility to Alzheimer’s disease. However, these studies have yielded contradictory results. Therefore, to resolve this issue, a meta-analysis was undertaken to examine 12 previously published studies. The pooled effect of CD33 rs3865444 showed no significant relationship with susceptibility to Alzheimer’s disease under various genetic models. The pooled effect of ABCA7 rs3764650 also lacked association with susceptibility to Alzheimer’s disease in the allele model (p = 0.06, OR = 1.06, 95% CI, 1.00-1.13), while significant associations were revealed for the dominant model (p < 0.0001 OR = 1.20, 95% CI, 1.10-1.31), recessive model (p = 0.01, OR = 1.59, 95% CI, 1.12-2.28), and additive model (p = 0.003, OR = 1.44, 95% CI, 1.13-1.83). A subsequent meta-analysis revealed significant association of these models for Caucasians (dominant: p < 0.00001, OR = 1.28, 95% CI, 1.16-1.41; recessive: p = 0.002, OR = 1.96, 95% CI, 1.27-3.04; additive: p = 0.001, OR = 1.96, 95% CI, 1.30-2.94), contrary to what was demonstrated for Asians. Results of the present meta-analysis indicate that ABCA7 rs3764650 might increase the risk of Alzheimer’s disease, particularly for older Caucasians.

Key words:  Alzheimer’s disease      single nucleotide polymorphisms      CD33 rs3865444      ABCA7 rs3764650      meta-analysis     
Submitted:  24 September 2017      Accepted:  20 November 2017      Published:  15 November 2018     
*Corresponding Author(s):  Qing Zhao     E-mail:  zhaoqing@jlu.edu.cn

Cite this article: 

Jing Wang, Xiangyi Kong, Lele Cong, Zhongxin Xu, Jianshi Du, Xianling Cong, Hongyan Sun, Yanan Xu, Qing Zhao. Associations between CD33 rs3865444 and ABCA7 rs3764650 polymorphisms and susceptibility to Alzheimer's disease. Journal of Integrative Neuroscience, 2018, 17(4): 313-321.

URL: 

https://jin.imrpress.com/EN/10.31083/j.jin.2018.04.0408     OR     https://jin.imrpress.com/EN/Y2018/V17/I4/313

Table 1  Characteristics of case-control studies for CD33 gene included in meta-analysis
First author Year Country Ethnicity Case Control HWE
CD33 rs3865444
Hollingworth(GERAD1) [22] 2011 Europe Caucasian 3333 1225 yes
Hollingworth(EADI1) [22] 2011 Europe Caucasian 2025 5328 yes
Hollingworth(deCODE) [22] 2011 Europe Caucasian 925 612 yes
Carrasquillo(Jacksonville) [29] 2011 USA Caucasian 492 920 yes
Carrasquillo(Rochester) [29] 2011 USA Caucasian 312 1577 yes
Carrasquillo(Autopsy) [29] 2011 USA Caucasian 298 97 yes
Carrasquillo(Norway) [29] 2011 Europe Caucasian 327 541 yes
Carrasquillo(Poland) [29] 2011 Europe Caucasian 467 187 yes
Carrasquillo(ARUK) [29] 2011 Europe Caucasian 642 730 yes
Deng [28] 2012 China Asian 190 193 yes
Chung [27] 2013 Korea Asian 290 554 yes
Tan [25] 2013 China Asian 612 612 yes
Omoumi [23] 2014 Canada Caucasian 580 524 yes
Walker [31] 2014 USA Caucasian 97 96 yes
Carrasquillo [33] 2014 USA Caucasian 135 2440 yes
Mao [30] 2015 China Asian 126 129 yes
Moreno [24] 2017 Colombia Caucasian 280 357 yes
HWE: Hardy-Weinberg equilibrium
Table 2  Characteristics of the case-control studies for ABCA7 gene included in meta-analysis
First author Year Country Ethnicity Case Control HWE
ABCA7 rs3764650
Harold [32] 2009 UK/Ireland Caucasian 2226 4704 no
Harold [32] 2009 Germany Caucasian 555 824 no
Harold [32] 2009 USA Caucasian 551 930 yes
Hollingworth(ADNI) [22] 2011 USA Caucasian 151 177 yes
Hollingworth(GERAD2) [22] 2011 UK Caucasian 3262 3320 yes
Hollingworth(deCODE) [22] 2011 Iceland Caucasian 925 612 yes
Hollingworth(AD-IG) [22] 2011 USA Caucasian 709 971 yes
Hollingworth(CHARGE) [22] 2011 Netherlands Caucasian 1239 10813 yes
Hollingworth(MAYO2) [22] 2011 USA Caucasian 2490 4114 yes
Hollingworth(EADI1) [22] 2011 France Caucasian 2751 2620 yes
Tan [25] 2013 China Asian 612 612 yes
Chung [27] 2013 Korea Asian 290 554 yes
Carrasqillo [33] 2014 America Caucasian 132 2486 yes
Liu [26] 2014 China Asian 350 283 yes
Omoumi [23] 2014 Canada Caucasian 580 524 yes
Moreno [24] 2017 Colombia Caucasian 280 357 yes
HWE: Hardy-Weinberg equilibrium
Fig. 1.  Forest plot of CD33 rs3865444 polymorphism association with AD using the allele model. M-H, Mantel-Haenszel, random effect model, confidence interval (CI).

Table 3  Meta-analysis of the CD33 rs3865444 polymorphisms with Alzheimer’s disease
CD33 rs3865444 polymorphism
Genetic model Cases/controls(n/n) Ethnicity No. of studies OR (95% CI) p-value I 2 (%)
allele (A vs. C) 22262/32244 Overall 10 1.00[0.92, 1.09] 0.99 71
2436/2976 Asian 4 1.10[0.66, 1.83] 0.71 92
19826/29268 Caucasian 6 0.98[0.93, 1.02] 0.26 0
Dominant(AA + AC vs. CC) 4052/8237 Overall 7 1.25[0.90, 1.73] 0.18 92
928/934 Asian 3 1.36[0.74, 2.51] 0.33 87
3124/7303 Caucasian 4 1.22[0.82, 1.81] 0.32 93
Recessive(AA vs. AC + CC) 4052/8293 Overall 7 1.21[0.93, 1.58] 0.15 65
928/934 Asian 3 1.11[0.49, 2.50] 0.8 73
3124/7359 Caucasian 4 1.09[0.87, 1.38] 0.45 50
Additive(AA vs. CC) 2686/4964 Overall 7 1.10[0.83, 1.44] 0.51 69
601/649 Asian 3 1.76[0.65, 4.81] 0.27 78
2085/4315 Caucasian 4 0.90[0.78, 1.03] 0.13 0
Fig. 2.  Forest plot of ABCA7 rs3764650 polymorphism association with AD using the allele model. M-H, Mantel-Haenszel, random effect model, confidence interval (CI).

Table 4  Meta-analysis of the ABCA7 rs3764650 polymorphisms with Alzheimer’s disease
ABCA7 rs3764650 polymorphism
Genetic model Cases/controls(n/n) Ethnicity No. of studies OR (95% CI) p-value I 2 (%)
allele(G vs. T) 52214/82948 Overall 8 1.06[1.00, 1.13] 0.06 49
2504/2898 Asian 3 1.06[0.94, 1.19] 0.33 0
49710/80050 Caucasian 5 1.06[0.99, 1.14] 0.1 59
Dominant(GG + GT vs. TT) 4995/10333 Overall 8 1.20[1.10, 1.31] <0.0001 30
962/895 Asian 3 1.00[0.83, 1.19] 0.96 0
4033/9438 Caucasian 5 1.28[1.16, 1.41] <0.00001 0
Recessive(GG vs. GT + TT) 4995/10333 Overall 8 1.59[1.12, 2.28] 0.01 44
962/895 Asian 3 1.34[0.79, 2.26] 0.28 70
4033/9438 Caucasian 5 1.96[1.27, 3.04] 0.002 9
Additive(GG vs. TT) 3886/8484 Overall 8 1.44[1.13, 1.83] 0.003 36
606/535 Asian 3 1.23[0.92, 1.66] 0.16 23
3280/7949 Caucasian 5 1.96[1.30, 2.94] 0.001 5
CD33: siglec-3; ABCA7: ATP-Bing Cassette, sub-family A; OR, odds ratio; CI, confidence interval
Fig. 3.  Forest plot of CD33 rs3865444 polymorphism association with AD using the allele model for different ethnicities. M-H, Mantel-Haenszel, rondom effct model, confidence interval (CI).

Fig. 4.  plot of ABCA7 rs3764650 polymorphism association with AD using the dominant model for different ethnicities. M-H, Mantel-Haenszel, random effect model, confidence interval (CI).

Fig. 5.  Publication bias for CD33 rs3865444 and ABCA7 rs3764650 under the allele model detected by Egger’s publication bias plot analysis.
SE:Standard error of mean.

[1] Ji H, Dai D, Wang Y, Jiang D, Zhou X, Lin P, Ji X, Li J, Zhang Y, Yin H, Chen R, Zhang L, Xu M, Duan S, Wang Q ( 2015) Association of BDNF and BCHE with Alzheimer’s disease: meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls. Experimental & Therapeutic Medicine 9(5), 1831-1840.
[2] Deng Y, Long L, Wang K, Zhou J, Zeng L, He L, Gong Q ( 2017) Icariside II, a broad-spectrum anti-cancer agent, reverses beta-amyloid-induced cognitive impairment through reducing inflammation and apoptosis in rats. Frontiers in Pharmacology 8, 39.
[3] Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, Jun G, DeStefano AL, Bis JC, Beecham GW ( 2013) Meta-analysis of 74, 046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nature Genetics 45(12), 1452-1458.
doi: 10.1038/ng.2802
[4] 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(4), 631-643.
[5] Malik M, Simpson JF, Parikh I, Wilfred BR, Fardo DW, Nelson PT, Estus S ( 2013) CD33 Alzheimer’s risk-altering polymorphism, CD33 expression, and exon 2 splicing. Journal of Neuroscience 33(33), 13320-13325.
[6] Linnartz B, Wang Y, Neumann H ( 2010) Microglial immunoreceptor tyrosine-based activation and inhibition motif signaling in neuroinflammation. International Journal of Alzheimer’s Disease 2010, 1703-1710.
doi: 10.4061/2010/587463 pmid: 20721346
[7] Karch CM, Goate AM ( 2015) Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biological Psychiatry 77(1), 43-51.
[8] Linnartz B, Neumann H ( 2013) Microglial activatory (immunoreceptor tyrosine-based activation motif)- and inhibitory (immunoreceptor tyrosine-based inhibition motif)- signaling receptors for recognition of the neuronal glycocalyx. Glia 61(1), 37-46.
doi: 10.1002/glia.22359 pmid: 22615186
[9] Jiang Q, Lee CD, Mandrekar S, Wilkinson B, Cramer P, Zelcer N, Mann K, Lamb B, Willson TM, Collins JL ( 2008) ApoE promotes the proteolytic degradation of Aβ. Neuron 58(5), 681-693.
doi: 10.1016/j.neuron.2008.04.010 pmid: 18549781
[10] Ikeda Y, Abe-Dohmae S, Munehira Y, Aoki R, Kawamoto S, Furuya A, Shitara K, Amachi T, Kioka N, Matsuo M ( 2003) Posttranscriptional regulation of human ABCA7 and its function for the apoA-I-dependent lipid release. Biochemical and Biophysical Research Communications 311(2), 313-318.
doi: 10.1016/j.bbrc.2003.10.002 pmid: 14592415
[11] Shulman JM, Chen K, Keenan BT, Chibnik LB, Fleisher A, Thiyyagura P, Roontiva A, McCabe C, Patsopoulos NA, Corneveaux JJ ( 2013) Genetic susceptibility for Alzheimer disease neuritic plaque pathology. JAMA Neurology 70(9), 1150-1157.
doi: 10.1001/jamaneurol.2013.2815
[12] Tanaka N, Abe-Dohmae S, Iwamoto N, Fitzgerald ML, Yokoyama S ( 2010) Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing atp-binding cassette transporter a7. Journal of Lipid Research 51(9), 2591-2599.
doi: 10.1194/jlr.M006049 pmid: 2918442
[13] Jehle AW, Gardai SJ, Li S, Linsel-Nitschke P, Morimoto K, Janssen WJ, Vandivier RW, Wang N, Greenberg S, Dale BM ( 2006) ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages. Journal of Cell Biolofy 174(4), 547-556.
[14] Wildsmith KR, Holley M, Savage JC, Skerrett R, Landreth GE ( 2013) Evidence for impaired amyloid β clearance in Alzheimer’s disease . Alzheimer’s Research & Therapy 5(4), 33.
[15] Kawalec P, Mikrut A, Wi s ' niewska N , Pilc A ( 2013) The effectiveness of tofacitinib, a novel Janus kinase inhibitor, in the treatment of rheumatoid arthritis: a systematic review and meta-analysis. Clinical Rheumatology 32(10), 1415-1424.
doi: 10.1007/s10067-013-2329-9
[16] Karch CM, Jeng AT, Nowotny P, Cady J, Cruchaga C, Goate AM ( 2012) Expression of novel Alzheimer’s disease risk genes in control and Alzheimer’s disease brains. Plos One 7(11), e50976.
doi: 10.1371/journal.pone.0050976 pmid: 23226438
[17] Vasquez JB, Fardo DW, Estus S ( 2013) ABCA7 expression is associated with Alzheimer’s disease polymorphism and disease status. Neuroscience Letters 556, 58-62.
[18] Chan SL, Kim WS, Kwok JB, Hill AF, Cappai R, Rye KA, Garner B ( 2008) ATP-binding cassette transporter A7 regulates processing of amyloid precursor protein in vitro. Journal of Neurochemistry 106(2), 793-804.
doi: 10.1111/j.1471-4159.2008.05433.x pmid: 18429932
[19] Kim WS, Guillemin GJ, Glaros EN, Lim CK, Garner B ( 2006) Quantitation of ATP-binding cassette subfamily-A transporter gene expression in primary human brain cells. Neuroreport 17(9), 891-896.
doi: 10.1097/01.wnr.0000221833.41340.cd pmid: 16738483
[20] Ben-Zeev O, Doolittle MH, Singh N, Chang CH, Schotz MC ( 1990) Synthesis and regulation of lipoprotein lipase in the hippocampus. Journal of Lipid Research 31(7), 1307-1313.
pmid: 2401861
[21] Egger M, Smith GD, Schneider M, Minder C ( 1997) Bias in meta-analysis detected by a simple, graphical test. British Medical Journal 315(7109), 629-634.
[22] Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM, Abraham R, Hamshere ML, Pahwa JS, Moskvina V ( 2011) Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nature Genetics 43(5), 429-435.
doi: 10.1038/ng.803 pmid: 3084173
[23] Omoumi A, Fok A, Greenwood T, Sadovnick AD, Feldman HH, Hsiung GYR ( 2014) Evaluation of late-onset Alzheimer disease genetic susceptibility risks in a Canadian population. Neurobiology of Aging 35(4), e912, e935-e936.
doi: 10.1016/j.neurobiolaging.2013.09.025 pmid: 24176626
[24] Moreno DJ, Ruiz S, Ríos Á, Lopera F, Ostos H, Via M, Bedoya G ( 2017) Association of GWAS top genes with late-onset Alzheimer’s disease in Colombian population. American Journal of Alzheimer’s Disease & Other Dementias 32(1), 27-35.
[25] 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. Alzheimer’s & Dementia 9(5), 546-553.
doi: 10.1016/j.jalz.2012.08.007 pmid: 23232270
[26] Liu LH, Xu J, Deng YL, Tang HD, Wang Y, Ren RJ, Xu W, Ma JF, Wang G, Chen SD ( 2014) A complex association of ABCA7 genotypes with sporadic Alzheimer disease in Chinese Han population. Alzheimer Disease & Associated Disorders 28(2), 141-144.
doi: 10.1097/WAD.0000000000000000 pmid: 24113560
[27] 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 Disease & Associated Disorders 27(3), 250-257.
doi: 10.1097/WAD.0b013e31826d7281 pmid: 22975751
[28] Deng YL, Liu LH, Wang Y, Tang HD, Ren RJ, Xu W, Ma JF, Wang LL, Zhuang JP, Wang G ( 2012) The prevalence of CD33 and MS4A6A variant in Chinese Han population with Alzheimer’s disease. Human Genetics 131(7), 1245-1249.
doi: 10.1007/s00439-012-1154-6
[29] Carrasquillo MM, Belbin O, Hunter TA, Ma L, Bisceglio GD, Zou F, Crook JE, Pankratz VS, Sando SB, Aasly JO ( 2011) Replication of EPHA1 and CD33 associations with late-onset Alzheimer’s disease: a multi-centre case-control study. Molecular Neurodegeneration 6(1), 54.
[30] Mao YF, Guo ZY, Pu JL, Chen YX, Zhang BR ( 2015) Association of CD33 and MS4A cluster variants with Alzheimer’s disease in East Asian populations. Neuroscience Letters 609, 235-239.
[31] Walker DG, Whetzel AM, Serrano G, Sue LI, Beach TG, Lue LF ( 2015) Association of CD33 polymorphism rs3865444 with Alzheimer’s disease pathology and CD33 expression in human cerebral cortex. Neurobiology of Aging 36(2), 571-582.
doi: 10.1016/j.neurobiolaging.2014.09.023 pmid: 4315751
[32] Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Williams A ( 2009) Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nature Genetics 41(10), 1088-1093.
[33] Carrasquillo MM, Murray ME, Krishnan S, Aakre J, Pankratz VS, Nguyen T, Ma L, Bisceglio G, Petersen RC, Younkin SG ( 2014) Late-onset Alzheimer disease genetic variants in posterior cortical atrophy and posterior AD. Neurology 82(16), 1455-1462.
doi: 10.1212/WNL.0000000000000335
[34] Bao J, Wang XJ, Mao ZF ( 2016) Associations between genetic variants in 19p13 and 19q13 regions and susceptibility to Alzheimer disease: A meta-analysis. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research 22, 234-243.
doi: 10.12659/MSM.895622 pmid: 4727495
[35] Li X, Shen N, Zhang S, Liu J, Jiang Q, Liao M, Feng R, Zhang L, Wang G, Ma G ( 2015) CD33 rs3865444 polymorphism contributes to Alzheimer’s disease susceptibility in Chinese, European, and North American populations. Molecular Neurobiology 52(1), 414-421.
[36] Bamji-Mirza M, Li Y, Najem D, Liu QY, Walker D, Lue LF, Stupak J, Chan K, Li J, Ghani M ( 2016) Genetic variations in ABCA7 can increase secreted levels of amyloid- β 40 and amyloid- β 42 peptides and ABCA7 transcription in cell culture models . Journal of Alzheimer’s Disease 53(3), 875-892.
doi: 10.3233/JAD-150965 pmid: 27314524
[37] Liu G, Li F, Zhang S, Jiang Y, Ma G, Shang H, Liu J, Feng R, Zhang L, Liao M ( 2014) Analyzing large-scale samples confirms the association between the ABCA7 rs3764650 polymorphism and Alzheimer’s disease susceptibility. Molecular Neurobiology 50(3), 757-764.
doi: 10.1007/s12035-014-8670-4 pmid: 24643655
[38] Cao H, Crocker PR ( 2011) Evolution of CD33-related siglecs: regulating host immune functions and escaping pathogen exploitation? Immunology 132(1), 18-26.
doi: 10.1111/j.1365-2567.2010.03368.x pmid: 21070233
[39] Pahnke J, Fröhlich C, Krohn M, Schumacher T, Paarmann K ( 2013) Impaired mitochondrial energy production and ABC transporter function-A crucial interconnection in dementing proteopathies of the brain. Mechanisms of Ageing and Development 134(10), 506-515.
doi: 10.1016/j.mad.2013.08.007 pmid: 24012632
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