Skip to main content

Advertisement

SpringerLink
Log in

Genetic polymorphism of interleukin 1β −511C/T and susceptibility to sporadic Alzheimer’s disease: a meta-analysis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

A large number of epidemiological studies have been performed to investigate the association between Alzheimer’s disease (AD) risk and interleukin-1β −511C/T genetic polymorphism, however, inconsistent results have been reported. The effect of the IL-1β −511C/T polymorphism on AD susceptibility was evaluated by a meta-analysis. Series of databases were researched. 14 studies involving 2640 AD case and 3493 control subjects were identified. The pooled results showed there were no statistical associations of interleukin-1β −511C/T genetic polymorphism with susceptibility to AD for five analysis models in all subjects. However, obvious heterogeneity among studies was detected. When stratifying for age at onset, ethnicity and geographic distribution of population to explore the original source of heterogeneity, the meta-analysis results based on geographic distribution of population showed the significant difference (CC vs CT, OR 1.26, 95 % CI: 1.03, 1.54, z = 2.25, P = 0.025; CC vs CT+TT, OR 1.24, 95 % CI: 1.03, 1.50, z = 2.24, P = 0.025) only in non-Europe. These findings indicate that the IL-1β −511C/T polymorphism might be associated with AD risk, and individuals with IL-1β −511C/C genotype might be at higher risk of AD in non-Europe. Further larger sample research would be warranted to confirm these conclusions.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. McGeer EG, McGeer PL (1998) The importance of inflammatory mechanisms in Alzheimer disease. Exp Gerontol 33:371–378

    Article  PubMed  CAS  Google Scholar 

  2. Griffin WS, Sheng JG, Royston MC, Gentleman SM, McKenzie JE, Graham DI, Roberts GW, Mrak RE (1998) Glial-neuronal interactions in Alzheimer’s disease: the potential role of a cytokine cycle in disease progression. Brain Pathol 8:65–72

    Article  PubMed  CAS  Google Scholar 

  3. Sheng JG, Mrak RE, Griffin WS (1997) Glial-neuronal interactions in Alzheimer’s disease: progressive association of IL-1a microglia and S100b astrocytes with neurofibrillary tangle stages. J Neuropathol Exp Neurol 56:285–290

    Article  PubMed  CAS  Google Scholar 

  4. Sheng JG, Mrak RE, Griffin WS (1995) Microglial interleukin-1a expression in brain regions in Alzheimer’s disease: correlation with neuritic plaque distribution. Neuropath Appl Neurol 21:290–301

    Article  CAS  Google Scholar 

  5. Cacabelos R, Barquero M, García P, Alvarez XA, Varela de Seijas E (1991) Cerebrospinal fluid interleukin-1beta (IL-1 beta) in Alzheimer’s disease and neurological disorders. Methods Find Exp Clin Pharmacol 13:455–458

    PubMed  CAS  Google Scholar 

  6. Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White CL 3rd, Araoz C (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 86:7611–7615

    Article  PubMed  CAS  Google Scholar 

  7. Dinarello CA (1996) Biological basis for interleukin 1 in disease. Blood 87:2095–2147

    PubMed  CAS  Google Scholar 

  8. Mattila KM, Rinne JO, Lehtimaki T, Roytta M, Ahonen JP, Hurme M (2002) Association of an interleukin 1B gene polymorphism (−511) with Parkinson’s disease in Finnish patients. J Med Genet 39:400–402

    Article  PubMed  CAS  Google Scholar 

  9. Grimaldi LME, Casadei VM, Ferri C, Veglia F, Licastro F, Annoni G, Biunno I, De-Bellis G, Sorbi S, Mariani C, Canal N, Griffin WST, Franceschi M (2000) Association of early-onset Alzheimer’s disease with an interleukin-1a gene polymorphism. Ann Neurol 47:361–365

    Article  PubMed  CAS  Google Scholar 

  10. Minster RL, Dekosky ST, Ganguli M, Belle S, Kamboh MI (2000) Genetic association studies of interleukin-1 (IL-1A and IL-1B) and interleukin-1 receptor antagonist genes and the risk of Alzheimer’s disease. Ann Neurol 48:817–819

    Article  PubMed  CAS  Google Scholar 

  11. Green EK, Harris JM, Lemmon H, Lambert JC, Chartier-Harlin MC, St Clair D, Mann DM, Iwatsubo T, Lendon CL (2002) Are interleukin-1 gene polymorphisms risk factors or disease modifiers in AD? Neurology 58:1566–1568

    Article  PubMed  CAS  Google Scholar 

  12. Licastro F, Pedrini S, Ferri C, Casadei V, Govoni M, Pession A, Sciacca FL, Veglia F, Annoni G, Bonafè M, Olivieri F, Franceschi C, Grimaldi LM (2000) Gene polymorphism affecting alpha1-antichymotrypsin and interleukin-1 plasma levels increases Alzheimer’s disease risk. Ann Neurol 48:388–391

    Article  PubMed  CAS  Google Scholar 

  13. Licastro F, Porcellini E, Caruso C, Lio D, Corder EH (2007) Genetic risk profiles for Alzheimer’s disease: integration of APOE genotype and variants that up-regulate inflammation. Neurobiol Aging 28:1637–1643

    Article  PubMed  CAS  Google Scholar 

  14. Bertram L, Blacker D, Crystal A, Mullin K, Keeney D, Jones J, Basu S, Yhu S, Guénette S, McInnis M, Go R, Tanzi R (2000) Candidate genes showing no evidence for association or linkage with Alzheimer’s disease using family-based methodologies. Exp Gerontol 35:1353–1361

    Article  PubMed  CAS  Google Scholar 

  15. Schjeide BM, McQueen MB, Mullin K, Divito J, Hogan MF, Parkinson M, Hooli B, Lange C, Blacker D, Tanzi RE, Bertram L (2009) Assessment of Alzheimer’s disease case-control associations using family-based methods. Neurogenetics 10:19–25

    Article  PubMed  Google Scholar 

  16. Giedraitis V, Kilander L, Degerman-Gunnarsson M, Sundelöf J, Axelsson T, Syvänen AC, Lannfelt L, Glaser A (2009) Genetic analysis of Alzheimer’s disease in the Uppsala Longitudinal Study of Adult Men. Dement Geriatr Cogn Disord 27:59–68

    Article  PubMed  Google Scholar 

  17. Rosenmann H, Meiner Z, Dresner-Pollak R, Kahana E, Aladjem Z, Grenader T, Wertman E, Abramsky O (2004) Lack of association of interleukin-1beta polymorphism with Alzheimer’s disease in the Jewish population. Neurosci Lett 363:131–133

    Article  PubMed  CAS  Google Scholar 

  18. Sciacca FL, Ferri C, Licastro F, Veglia F, Biunno I, Gavazzi A, Calabrese E, Martinelli Boneschi F, Sorbi S, Mariani C, Franceschi M, Grimaldi LM (2003) Interleukin-1B polymorphism is associated with age at onset of Alzheimer’s disease. Neurobiol Aging 24:927–931

    Article  PubMed  CAS  Google Scholar 

  19. Nicoll JA, Mrak RE, Graham DI, Stewart J, Wilcock G, MacGowan S, Esiri MM, Murray LS, Dewar D, Love S, Moss T, Griffin WS (2000) Association of interleukin-1 gene polymorphisms with Alzheimer’s disease. Ann Neurol 47:365–368

    Article  PubMed  CAS  Google Scholar 

  20. Oliveira JR, Nishimura AL, Lemos RR, Zatz M (2009) The genetics of Alzheimer’s disease in Brazil: 10 years of analysis in a unique population. J Mol Neurosci 37:74–79

    Article  PubMed  CAS  Google Scholar 

  21. Hedley R, Hallmayer J, Groth DM, Brooks WS, Gandy SE, Martins RN (2002) Association of interleukin-1 polymorphisms with Alzheimer’s disease in Australia. Ann Neurol 51:795–797

    Article  PubMed  CAS  Google Scholar 

  22. Ehl C, Kölsch H, Ptok U, Jessen F, Schmitz S, Frahnert C, Schlösser R, Rao ML, Maier W, Heun R (2003) Association of an interleukin-1beta gene polymorphism at position −511 with Alzheimer’s disease. Int J Mol Med 11:235–238

    PubMed  CAS  Google Scholar 

  23. Wang WF, Liao YC, Wu SL, Tsai FJ, Lee CC, Hua CS (2005) Association of interleukin-I beta and receptor antagonist gene polymorphisms with late onset Alzheimer’s disease in Taiwan Chinese. Eur J Neurol 12:609–613

    Article  PubMed  Google Scholar 

  24. Ravaglia G, Paola F, Maioli F, Martelli M, Montesi F, Bastagli L, Bianchin M, Chiappelli M, Tumini E, Bolondi L, Licastro F (2006) Interleukin-1b and interleukin-6 gene polymorphisms as risk factors for AD: a prospective study. Exp Gerontol 41:85–92

    Article  PubMed  CAS  Google Scholar 

  25. Wang HK, Hsu WC, Fung HC, Lin JC, Hsu HP, Wu YR, Hsu Y, Hu FJ, Lee-Chen GJ, Chen CM (2007) Interleukin-1a and -1b promoter polymorphisms in Taiwanese patients with dementia. Dement Geriatr Cogn Disord 24:104–110

    Article  PubMed  CAS  Google Scholar 

  26. Déniz-Naranjo MC, Muñoz-Fernandez C, Alemany-Rodríguez MJ, Pérez-Vieitez MC, Aladro-Benito Y, Irurita-Latasa J, Sánchez-García F (2008) Cytokine IL-1beta but not IL-1alpha promoter polymorphism is associated with Alzheimer disease in a population from the Canary Islands, Spain. Eur J Neurol 15:1080–1084

    Article  PubMed  Google Scholar 

  27. Klimkowicz-Mrowiec A, Marona M, Wołkow P, Maruszak A, Styczynska M, Barcikowska M, Zekanowski C, Szczudlik A, Slowik A (2009) Interleukin-1 gene –511CT polymorphism and the risk of Alzheimer’s disease in a polish population. Dement Geriatr Cogn Disord 28:461–464

    Article  PubMed  CAS  Google Scholar 

  28. Wehr H, Bednarska-Makaruk M, Łojkowska W, Graban A, Hoffman-Zacharska D, Kuczyńska-Zardzewiały A, Mrugała J, Rodo M, Bochyńska A, Sułek A, Ryglewicz D (2006) Differences in risk factors for dementia with neurodegenerative traits and for vascular dementia. Dement Geriatr Cogn Disord 22:1–7

    Article  PubMed  CAS  Google Scholar 

  29. McCulley MC, Day IN, Holmes C (2004) Association between interleukin 1-beta promoter (−511) polymorphism and depressive symptoms in Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet 124B:50–53

    Article  PubMed  Google Scholar 

  30. Ma SL, Tang NL, Lam LC, Chiu HF (2003) Lack of association of the interleukin-1b gene polymorphism with Alzheimer’s disease in a Chinese population. Dement Geriatr Cogn Disord 16:265–268

    Article  PubMed  CAS  Google Scholar 

  31. Bosco P, Guéant-Rodríguez RM, Anello G, Romano A, Namour B, Spada RS, Caraci F, Tringali G, Ferri R, Guéant JL (2004) Association of IL-1 RN*2 allele and methionine synthase 2756 AA genotype with dementia severity of sporadic Alzheimer’s disease. J Neurol Neurosurg Psychiatry 75:1036–1038

    Article  PubMed  CAS  Google Scholar 

  32. Yucesoy B, Peila R, White LR, Wu KM, Johnson VJ, Kashon ML, Luster MI, Launer LJ (2006) Association of interleukin-1 gene polymorphisms with dementia in a community-based sample: the Honolulu-Asia aging study. Neurobiol Aging 27:211–217

    Article  PubMed  CAS  Google Scholar 

  33. Li XQ, Zhang JW, Zhang ZX, Chen D, Qu QM (2004) Interleukin-1 gene cluster polymorphisms and risk of Alzheimer’s disease in Chinese Han population. J Neural Transm 111:1183–1190

    Article  PubMed  CAS  Google Scholar 

  34. Nishimura M, Sakamoto T, Kaji R, Kawakami H (2004) Influence of polymorphisms in the genes for cytokines and glutathione S-transferase omega on sporadic Alzheimer’s disease. Neurosci Lett 368:140–143

    Article  PubMed  CAS  Google Scholar 

  35. Seripa D, Matera MG, Dal Forno G, Gravina C, Masullo C, Daniele A, Binetti G, Bonvicini C, Squitti R, Palermo MT, Davis DG, Antuono P, Wekstein DR, Dobrina A, Gennarelli M, Fazio VM (2005) Genotypes and haplotypes in the IL-1 gene cluster: analysis of two genetically and diagnostically distinct groups of Alzheimer patients. Neurobiol Aging 26:455–464

    Article  PubMed  CAS  Google Scholar 

  36. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-A DRDA work group under the auspices of department of health and human services task force on alzheimer’s disease. Neurology 34:939–944

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Rehabilitation Medicine, The Second People’s Hospital of Hefei City, 246th Heping Road, Hefei, 230011, Anhui Province, China

    Hai Yuan, Qing Xia, Pingping Ge & Shaowei Wu

Authors
  1. Hai Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qing Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pingping Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shaowei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hai Yuan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yuan, H., Xia, Q., Ge, P. et al. Genetic polymorphism of interleukin 1β −511C/T and susceptibility to sporadic Alzheimer’s disease: a meta-analysis. Mol Biol Rep 40, 1827–1834 (2013). https://doi.org/10.1007/s11033-012-2237-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-2237-0

Keywords

Search

Navigation