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CLU rs2279590 polymorphism contributes to Alzheimer’s disease susceptibility in Caucasian and Asian populations

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

It is reported that CLU rs2279590 polymorphism is significantly associated with Alzheimer’s disease (AD) in European ancestry. Recent studies investigated rs2279590 polymorphism in Asian population (Chinese, Japanese and Korean). Four studies showed negative association and two studies showed weak association between rs2279590 and AD. We believe that the weak association or no association may be caused by the relatively small sample size in Asian population. Here, we reinvestigated the association in Asian population. Meanwhile, to investigate the genetic heterogeneity of the rs2279590 polymorphism in Asian and Caucasian populations, we searched the PubMed and AlzGene databases and selected 11 independent studies (6 studies in Asian population and 5 studies in Caucasian population) including 20,655 individuals (8,605 cases and 12,050 controls) for meta-analysis. Our results showed significant association between rs2279590 polymorphism and AD in Asian population with P = 2.00E−04 and P = 2.00E−04 using additive and recessive models, respectively. We observed no significant heterogeneity between Asian and Caucasian populations. We believe that our results may be helpful to understand the mechanisms of CLU in AD pathogenesis and will be useful for future genetic studies in AD.

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References

  • Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265

    Article  CAS  PubMed  Google Scholar 

  • Braskie MN, Jahanshad N, Stein JL, Barysheva M, McMahon KL, de Zubicaray GI et al (2011) Common Alzheimer’s disease risk variant within the CLU gene affects white matter microstructure in young adults. J Neurosci 31(18):6764–6770

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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(8):961–964

    Article  PubMed Central  PubMed  Google Scholar 

  • 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(1):210 (e211–217)

    Article  CAS  PubMed  Google Scholar 

  • Daimon M, Oizumi T, Karasawa S, Kaino W, Takase K, Tada K et al (2011) Association of the clusterin gene polymorphisms with type 2 diabetes mellitus. Metabolism 60(6):815–822

    Article  CAS  PubMed  Google Scholar 

  • Elias-Sonnenschein LS, Helisalmi S, Natunen T, Hall A, Paajanen T, Herukka SK et al (2013) Genetic loci associated with Alzheimer’s disease and cerebrospinal fluid biomarkers in a Finnish case-control cohort. PLoS ONE 8(4):e59676

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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(10):1088–1093

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM et al (2011) Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet 43(5):429–435

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jiang Y, Zhang R, Zheng J, Liu P, Tang G, Lv H et al (2012) Meta-analysis of 125 rheumatoid arthritis-related single nucleotide polymorphisms studied in the past two decades. PLoS ONE 7(12):e51571

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jin C, Li W, Yuan J, Xu W, Cheng Z (2012) Association of the CR1 polymorphism with late-onset Alzheimer’s disease in Chinese Han populations: a meta-analysis. Neurosci Lett 527(1):46–49

    Article  CAS  PubMed  Google Scholar 

  • Kamboh MI, Minster RL, Demirci FY, Ganguli M, Dekosky ST, Lopez OL et al (2012) Association of CLU and PICALM variants with Alzheimer’s disease. Neurobiol Aging 33(3):518–521

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Komatsu M, Shibata N, Kuerban B, Ohnuma T, Baba H, Arai H (2011) Genetic association between clusterin polymorphisms and Alzheimer’s disease in a Japanese population. Psychogeriatrics 11(1):14–18

    Article  PubMed  Google Scholar 

  • 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(10):1094–1099

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Liu G, Zhang L, Feng R, Liao M, Jiang Y, Chen Z et al (2013a) Lack of association between PICALM rs3851179 polymorphism and Alzheimer’s disease in Chinese population and APOEepsilon4-negative subgroup. Neurobiol Aging 34(4):1310 (e1319–1310)

    Article  CAS  PubMed  Google Scholar 

  • Liu G, Zhang S, Cai Z, Li Y, Cui L, Ma G et al (2013b) BIN1 gene rs744373 polymorphism contributes to Alzheimer’s disease in East Asian population. Neurosci Lett 544:47–51

    Article  CAS  PubMed  Google Scholar 

  • Liu G, Zhang S, Cai Z, Ma G, Zhang L, Jiang Y et al (2013c) PICALM gene rs3851179 Polymorphism contributes to Alzheimer’s disease in an Asian population. Neuromol Med 15(2):384–388

    Article  CAS  Google Scholar 

  • Liu G, Wang H, Liu J, Li J, Li H, Ma G et al (2014a) The CLU gene rs11136000 variant is significantly associated with Alzheimer’s disease in Caucasian and Asian populations. Neuromolecular Med 16(1):52–60

    Article  CAS  PubMed  Google Scholar 

  • Liu G, Yao L, Liu J, Jiang Y, Ma G, Chen Z et al (2014b) Cardiovascular disease contributes to Alzheimer’s disease: evidence from large-scale genome-wide association studies. Neurobiol Aging 35(4):786–792

    Article  PubMed  Google Scholar 

  • Logue MW, Schu M, Vardarajan BN, Buros J, Green RC, Go RC et al (2011) A comprehensive genetic association study of Alzheimer disease in African Americans. Arch Neurol 68(12):1569–1579

    Article  PubMed Central  PubMed  Google Scholar 

  • Miyashita A, Koike A, Jun G, Wang LS, Takahashi S, Matsubara E et al (2013) SORL1 is genetically associated with late-onset Alzheimer’s disease in Japanese, Koreans and Caucasians. PLoS One 8(4):e58618

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Naj AC, Jun G, Beecham GW, Wang LS, Vardarajan BN, Buros J et al (2011) Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet 43(5):436–441

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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(18):1832–1840

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sweet RA, Seltman H, Emanuel JE, Lopez OL, Becker JT, Bis JC et al (2012) Effect of Alzheimer’s disease risk genes on trajectories of cognitive function in the Cardiovascular Health Study. Am J Psychiatry 169(9):954–962

    Article  PubMed Central  PubMed  Google Scholar 

  • Thambisetty M, Beason-Held LL, An Y, Kraut M, Nalls M, Hernandez DG et al (2013) Alzheimer risk variant CLU and brain function during aging. Biol Psychiatry 73(5):399–405

    Article  PubMed Central  PubMed  Google Scholar 

  • Trikalinos TA, Salanti G, Khoury MJ, Ioannidis JP (2006) Impact of violations and deviations in Hardy–Weinberg equilibrium on postulated gene-disease associations. Am J Epidemiol 163(4):300–309

    Article  PubMed  Google Scholar 

  • Yu JT, Tan L (2012) The role of clusterin in Alzheimer’s disease: pathways, pathogenesis, and therapy. Mol Neurobiol 45(2):314–326

    Article  CAS  PubMed  Google Scholar 

  • Yu JT, Li L, Zhu QX, Zhang Q, Zhang W, Wu ZC et al (2010) Implication of CLU gene polymorphisms in Chinese patients with Alzheimer’s disease. Clin Chim Acta 411(19–20):1516–1519

    Article  CAS  PubMed  Google Scholar 

  • Yu JT, Ma XY, Wang YL, Sun L, Tan L, Hu N (2013) Genetic variation in clusterin gene and Alzheimer’s disease risk in Han Chinese. Neurobiol Aging 34(7):1921 (e1917–1923)

    Article  PubMed  Google Scholar 

  • Zhang MD, Gu W, Qiao SB, Zhu EJ, Zhao QM, Lv SZ (2014) Apolipoprotein e gene polymorphism and risk for coronary heart disease in the Chinese population: a meta-analysis of 61 studies including 6634 cases and 6393 controls. PLoS ONE 9(4):e95463

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

We thank Yu, Chen, KOMATSU and Lambert et al. for the genotype data. This work was supported by funding from the National Nature Science Foundation of China (grant numbers 81300945, 31200934, 31171219, 81271213, 81070878, 81271214, and 81261120404), the Natural Science Foundation of Guangdong Province, China (No S2012010008222), and the Science and Technology Innovation Fund of Guangdong Medical College (No. STIF 201101).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, The Forth Affiliated Hospital of Harbin Medical University, Harbin, China

    Shuyan Zhang & Hong Shang

  2. Department of Neurosurgery, The First Hospital of Harbin, 151 Diduan Street, Daoli Region, Harbin, China

    Donghui Zhang & Jiafeng Liu

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

    Yongshuai Jiang & Mingzhi Liao

  4. Department of Laboratory Medicine, Shengjing Hospital, China Medical University, Shenyang, China

    Lina Wu & Yong Liu

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

    Rennan Feng

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

    Liangcai Zhang

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

    Keshen Li

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

    Guiyou Liu

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  1. Shuyan Zhang
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  2. Donghui Zhang
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  3. Yongshuai Jiang
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  9. Liangcai Zhang
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  10. Yong Liu
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  11. Guiyou Liu
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Corresponding authors

Correspondence to Guiyou Liu or Keshen Li.

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Zhang, S., Zhang, D., Jiang, Y. et al. CLU rs2279590 polymorphism contributes to Alzheimer’s disease susceptibility in Caucasian and Asian populations. J Neural Transm 122, 433–439 (2015). https://doi.org/10.1007/s00702-014-1260-9

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  • DOI: https://doi.org/10.1007/s00702-014-1260-9

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