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

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.

[1]  Bin Zhao,et al.  The CLU Gene rs11136000 Variant is Significantly Associated with Alzheimer’s Disease in Caucasian and Asian Populations , 2013, NeuroMolecular Medicine.

[2]  Yongshuai Jiang,et al.  Meta-Analysis of 125 Rheumatoid Arthritis-Related Single Nucleotide Polymorphisms Studied in the Past Two Decades , 2012, PloS one.

[3]  G. Wang,et al.  The prevalence of CD33 and MS4A6A variant in Chinese Han population with Alzheimer’s disease , 2012, Human Genetics.

[4]  Nick C Fox,et al.  Common variants at ABCA 7 , MS 4 A 6 A / MS 4 A 4 E , EPHA 1 , CD 33 and CD 2 AP are associated with Alzheimer ’ s disease , 2011 .

[5]  Robert C Green,et al.  A comprehensive genetic association study of Alzheimer disease in African Americans. , 2011, Archives of neurology.

[6]  Ammarin Thakkinstian,et al.  Methods for meta-analyses of genome-wide association studies: critical assessment of empirical evidence. , 2012, American journal of epidemiology.

[7]  Wei Wang,et al.  Association of GWAS-linked loci with late-onset Alzheimer's disease in a northern Han Chinese population , 2013, Alzheimer's & Dementia.

[8]  H. Feldman,et al.  Evaluation of late-onset Alzheimer disease genetic susceptibility risks in a Canadian population , 2014, Neurobiology of Aging.

[9]  Rui-ping Liu,et al.  Re: “PICALM Gene rs3851179 Polymorphism Contributes to Alzheimer’s Disease in an Asian Population” , 2016, Neuromolecular medicine.

[10]  David A Bennett,et al.  CD33: increased inclusion of exon 2 implicates the Ig V-set domain in Alzheimer's disease susceptibility. , 2014, Human molecular genetics.

[11]  Bin Zhao,et al.  Cardiovascular disease contributes to Alzheimer's disease: evidence from large-scale genome-wide association studies , 2014, Neurobiology of Aging.

[12]  Nick C Fox,et al.  Common variants in ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease , 2011, Nature Genetics.

[13]  Yong Liu,et al.  CLU rs2279590 polymorphism contributes to Alzheimer’s disease susceptibility in Caucasian and Asian populations , 2015, Journal of Neural Transmission.

[14]  Jo Knight,et al.  Introduction to genetic association studies. , 2012, Cold Spring Harbor protocols.

[15]  D. G. Clark,et al.  Common variants at MS 4 A 4 / MS 4 A 6 E , CD 2 AP , CD 33 and EPHA 1 are associated with late-onset Alzheimer ’ s disease , 2011 .

[16]  J. Haines,et al.  SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians , 2013, PloS one.

[17]  Bradley T. Hyman,et al.  Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta , 2013, Neuron.

[18]  Zugen Chen,et al.  An Updated Analysis with 85,939 Samples Confirms the Association Between CR1 rs6656401 Polymorphism and Alzheimer’s Disease , 2014, Molecular Neurobiology.

[19]  D. G. Clark,et al.  Common variants in MS4A4/MS4A6E, CD2uAP, CD33, and EPHA1 are associated with late-onset Alzheimer’s disease , 2011, Nature Genetics.

[20]  Keith A. Johnson,et al.  CD33 Alzheimer’s disease locus: Altered monocyte function and amyloid biology , 2013, Nature Neuroscience.

[21]  Yongshuai Jiang,et al.  Analyzing Large-Scale Samples Confirms the Association Between the ABCA7 rs3764650 Polymorphism and Alzheimer’s Disease Susceptibility , 2014, Molecular Neurobiology.

[22]  V. Pankratz,et al.  Replication of EPHA1 and CD33 associations with late-onset Alzheimer's disease: a multi-centre case-control study , 2011, Molecular Neurodegeneration.

[23]  Zugen Chen,et al.  Cell adhesion molecules contribute to Alzheimer’s disease: multiple pathway analyses of two genome‐wide association studies , 2012, Journal of neurochemistry.

[24]  Mingzhi Liao,et al.  BIN1 gene rs744373 polymorphism contributes to Alzheimer's disease in East Asian population , 2013, Neuroscience Letters.

[25]  Zugen Chen,et al.  Lack of association between PICALM rs3851179 polymorphism and Alzheimer's disease in Chinese population and APOEε4-negative subgroup , 2013, Neurobiology of Aging.

[26]  Nick C Fox,et al.  Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease , 2013, Nature Genetics.

[27]  S. Chung,et al.  Association of GWAS Top Hits With Late-onset Alzheimer Disease in Korean Population , 2013, Alzheimer disease and associated disorders.