Skip to main content

Advertisement

Log in

VNTR polymorphisms of the IL-4 and IL-1RN genes and their relationship with frailty syndrome in Mexican community-dwelling elderly

  • Original Article
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

Inflammation is a key event that is closely associated with the pathophysiology of frailty. The relationship of genetic polymorphisms into inflammatory cytokines with frailty remains poorly understood. The aim of this study was to investigate the association between VNTR polymorphisms of the IL-4 and IL-1RN genes with the risk of frailty. We included a sample of 630 community-dwelling elderly aged 70 and older. Both IL-4 and IL-1RN VNTR polymorphisms were genotyped by the polymerase chain reaction (PCR) method. Mean age was 77.7 years (SD = 6.0) and 52.5 % were women. The participants classified as frail were more likely to be older, had lower MMSE score (p < 0.001), and had more disability for IADL (p < 0.001) and ADL (p < 0.001). Genotypic and allelic frequencies for the IL-4 VNTR polymorphism did not show significant differences between study groups (p > 0.05). However, we just observed a significant difference in the allelic frequencies for the A2 allele of the IL-1RN VNTR polymorphism between frail and nonfrail groups (OR 1.84, 95 % CI 1.08–3.12, p = 0.02). In addition, we analyzed the combined effect of the IL-4 and IL-1RN VNTR polymorphisms and their possible association with frailty, where the combined IL-4 lowIL-1Ra high genotype was identified as a marker of risk to frailty syndrome (OR 7.86, 95 % CI 1.83–33.69, p = 0.006). Our results suggest that both A2 allele and the combined IL-4 lowIL-1Ra high genotype might be genetic markers of susceptibility to frailty in Mexican elderly.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Chen X, Mao G, Leng SX (2014) Frailty syndrome: an overview. Clin Interv Aging 9:433–441

    PubMed  PubMed Central  Google Scholar 

  2. Leng SX, Xue QL, Tian J, Walston JD, Fried LP (2007) Inflammation and frailty in older women. J Am Geriatr Soc 55:864–871

    Article  PubMed  Google Scholar 

  3. Hubbard RE, O’Mahony MS, Savva GM, Calver BL, Woodhouse KW (2009) Inflammation and frailty measures in older people. J Cell Mol Med 13:3103–3109

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zaslavsky O, Cochrane BB, Thompson HJ, Woods NF, Herting JR, LaCroix A (2013) Frailty: a review of the first decade of research. Biol Res Nurs 15:422–432

    Article  PubMed  Google Scholar 

  5. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K (2013) Frailty in elderly people. Lancet 381:752–762

    Article  PubMed  Google Scholar 

  6. Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafè M, Cavallone L, Franceschi C, Caruso C (2002) Gender-specific association between -1082 IL-10 promoter polymorphism and longevity. Genes Immun 3:30–33

    Article  CAS  PubMed  Google Scholar 

  7. Cavallone L, Bonafè M, Olivieri F, Cardelli M, Marchegiani F, Giovagnetti S, Di Stasio G, Giampieri C, Mugianesi E, Stecconi R, Sciacca F, Grimaldi LM, De Benedictis G, Lio D, Caruso C, Franceschi C (2003) The role of IL-1 gene cluster in longevity: a study in Italian population. Mech Ageing Dev 124:533–538

    Article  CAS  PubMed  Google Scholar 

  8. Ho YY, Matteini AM, Beamer B, Fried L, Xue QL, Arking DE, Chakravarti A, Fallin MD, Walston J (2011) Exploring biologically relevant pathways in frailty. J Gerontol A Biol Sci Med Sci 66:975–979

    Article  PubMed  Google Scholar 

  9. Tong YQ, Ye JJ, Wang ZH, Zhang YW, Zhan FX, Guan XH, Geng YJ, Hou SY, Li Y, Cheng JQ, Lu ZX, Liu JF (2013) Association of variable number of tandem repeat polymorphism in the IL-4 gene with ischemic stroke in the Chinese Uyghur population. Genet Mol Res 12:2423–2431

    Article  PubMed  Google Scholar 

  10. Mittal RD, Manchanda PK (2007) Association of interleukin (IL)-4 intron-3 and IL-6—174 G/C gene polymorphism with susceptibility to end-stage renal disease. Immunogenetics 59:159–165

    Article  CAS  PubMed  Google Scholar 

  11. Vasudevan R, Norhasniza MN, Patimah I (2011) Association of variable number of tandem repeats polymorphism in the IL-4 gene with end-stage renal disease in Malaysian patients. Genet Mol Res 10:943–947

    Article  CAS  PubMed  Google Scholar 

  12. Inanir A, Yigit S, Tekcan A, Tural S, Kismali G (2013) IL-4 and MTHFR gene polymorphism in rheumatoid arthritis and their effects. Immunol Lett 152:104–108

    Article  CAS  PubMed  Google Scholar 

  13. Duan Y, Pan C, Shi J, Chen H, Zhang S (2014) Association between interleukin-4 gene intron 3 VNTR polymorphism and cancer risk. Cancer Cell Int 14:131

    Article  PubMed  PubMed Central  Google Scholar 

  14. Salimi S, Mohammadoo-Khorasani M, Yaghmaei M, Mokhtari M, Moossavi M (2014) Possible association of IL-4 VNTR polymorphism with susceptibility to preeclampsia. Biomed Res Int 2014:497031

    PubMed  PubMed Central  Google Scholar 

  15. Mout R, Willemze R, Landegent JE (1991) Repeat polymorphisms in the interleukin-4 gene (IL4). Nucleic Acids Res 19:3763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nakashima H, Miyake K, Inoue Y, Shimizu S, Akahoshi M, Tanaka Y, Otsuka T, Harada M (2002) Association between IL-4 genotype and IL-4 production in the Japanese population. Genes Immun 3:107–109

    Article  CAS  PubMed  Google Scholar 

  17. Korthagen NM, van Moorsel CH, Kazemier KM, Ruven HJ, Grutters JC (2012) IL1RN genetic variations and risk of IPF: a meta-analysis and mRNA expression study. Immunogenetics 64:371–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hashemi M, Naderi M, Ebrahimi M, Amininia S, Bahari G, Taheri M, Eskandari-Nasab E, Ghavami S (2015) Association between interleukin-1 receptor antagonist (IL1RN) variable number of tandem repeats (VNTR) polymorphism and pulmonary tuberculosis. Iran J Allergy Asthma Immunol 14:55–59

    PubMed  Google Scholar 

  19. Arend WP (2002) The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Factor Rev 13:323–340

    Article  CAS  PubMed  Google Scholar 

  20. Qian N, Chen X, Han S, Qiang F, Jin G, Zhou X, Dong J, Wang X, Shen H, Hu Z (2010) Circulating IL- 1β levels, polymorphisms of IL-1B, and risk of cervical cancer in Chinese women. J Cancer Res Clin Oncol 136:709–716

    Article  CAS  PubMed  Google Scholar 

  21. Zhang Y, Liu C, Peng H, Zhang J, Feng Q (2012) IL1 receptor antagonist gene IL1-RN variable number of tandem repeats polymorphism and cancer risk: a literature review and meta-analysis. PLoS One 7:e46017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tong Y, Han J, Guan X, Lu Z, Miao X, Ye J, Hou SY, Zhang Y, Geng Y, Li Y, Zhan F, Liu J, Cheng JQ (2013) Association of IL-1 receptor antagonist gene VNTR polymorphism with ischemic stroke in the Chinese Uyghur population. Biochem Genet 51:698–706

    Article  CAS  PubMed  Google Scholar 

  23. Ávila-Funes JA, Pina-Escudero SD, Aguilar-Navarro S, Gutierrez-Robledo LM, Ruiz-Arregui L, Amieva H (2011) Cognitive impairment and low physical activity are the components of frailty more strongly associated with disability. J Nutr Health 15:683–689

    Google Scholar 

  24. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA, Cardiovascular Health Study Collaborative Research Group (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56:M146–M156

    Article  CAS  PubMed  Google Scholar 

  25. Radloff LS (1997) The CES-D Scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1:385–401

    Article  Google Scholar 

  26. Washburn RA, McAuley E, Katula J, Mihalko SL, Boileau RA (1999) The physical activity scale for the elderly (PAse): evidence for validity. J Clin Epidemiol 52:643–651

    Article  CAS  PubMed  Google Scholar 

  27. Anovazzi G, Kim YJ, Viana AC, Curtis KM, Orrico SR, Cirelli JA, Scarel-Caminaga RM (2010) Polymorphisms and haplotypes in the interleukin-4 gene are associated with chronic periodontitis in a Brazilian population. J Periodontol 81:392–402

    Article  CAS  PubMed  Google Scholar 

  28. Tarlow JK, Blakemore AI, Lennard A, Solari R, Hughes HN, Steinkasserer A, Duff GW (1993) Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet 91:403–404

    Article  CAS  PubMed  Google Scholar 

  29. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  CAS  PubMed  Google Scholar 

  30. Katz S, Downs TD, Cash HR, Grotz RC (1970) Progress in development of the index of ADL. Gerontologist 10:20–30

    Article  CAS  PubMed  Google Scholar 

  31. Lawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186

    Article  CAS  PubMed  Google Scholar 

  32. Lewis PO, Zaykin D (2002) Genetic data analysis: computer program for the analysis of allelic data. Version 1.1. http://hydrodictyon.eeb.uconn.edu/people/plewis/software.php

  33. Bid HK, Konwar R, Agrawal CG, Banerjee M (2008) Association of IL-4 and IL-1RN (receptor antagonist) gene variants and the risk of type 2 diabetes mellitus: a study in the north Indian population. Indian J Med Sci 62:259–266

    Article  PubMed  Google Scholar 

  34. Arman A, Soylu O, Yildirim A, Furman A, Ercelen N, Aydogan H, Coker A, Tezel T (2008) Interleukin-1 receptor antagonist gene VNTR polymorphism is associated with coronary artery disease. Arq Bras Cardiol 91:293–298

    Article  CAS  PubMed  Google Scholar 

  35. Wang GC, Casolaro V (2014) Immunologic changes in frail older adults. Transl Med UniSa 9:1–6

    PubMed  PubMed Central  Google Scholar 

  36. Gallucci M, Ongaro F, Amici GP, Regini C (2009) Frailty, disability and survival in the elderly over the age of seventy: evidence from “The Treviso Longeva (TRELONG) Study”. Arch Gerontol Geriatr 48:281–283

    Article  CAS  PubMed  Google Scholar 

  37. Mora M, Sánchez L, Serra-Prat M, Palomera E, Blanco J, Aranda G, Falcón I, Cadenas I, Boquet X, Oriola J, Puig-Domingo M, Mataró Ageing Study Group (2012) Hormonal determinants and effect of ER22/23EK glucocorticoid receptor gene polymorphism on health status deterioration in the participants of the Mataró Ageing Study. Age Dordr 34:553–561

    Article  CAS  PubMed  Google Scholar 

  38. Almeida OP, Norman PE, van Bockxmeer FM, Hankey GJ, Flicker L (2012) CRP 1846G> A polymorphism increases risk of frailty. Maturitas 71:261–266

    Article  CAS  PubMed  Google Scholar 

  39. Walston J, Fedarko N, Yang H, Leng S, Beamer B, Espinoza S, Lipton A, Zheng H, Becker K (2008) The physical and biological characterization of a frail mouse model. J Gerontol 63:391–398

    Article  Google Scholar 

  40. Moore AZ, Biggs ML, Matteini A, O’Connor A, McGuire S, Beamer BA, Fallin MD, Fried LP, Walston J, Chakravarti A, Arking DE (2010) Polymorphisms in the mitochondrial DNA control region and frailty in older adults. PLoS One 5:e11069

    Article  PubMed  PubMed Central  Google Scholar 

  41. Matteini AM, Walston JD, Fallin MD, Bandeen-Roche K, Kao WH, Semba RD, Allen RH, Guralnik J, Fried LP, Stabler SP (2008) Markers of B-vitamin deficiency and frailty in older women. J Nutr Health Aging 12:303–308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Matteini AM, Walston JD, Bandeen-Roche K, Arking DE, Allen RH, Fried LP, Chakravarti A, Stabler SP, Fallin MD (2010) Transcobalamin-II variants, decreased vitamin B12 availability and increased risk of frailty. J Nutr Health Aging 14:73–77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors greatly appreciate the participation in this study of Jesús Lázaro López-Vázquez, laboratory assistant.

Funding

This study was supported by the National Institute of Geriatrics under the Grant Agreement No. DI-PI-003/2012.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nora Magdalena Torres-Carrillo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest related to the publication of this manuscript.

Ethical approval

The “Coyoacan Cohort” study protocol and the informed consent format were approved by the Ethical Committees of the Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” (INCMNSZ) and the Instituto Nacional de Salud Pública (INSP) of Mexico City. Likewise, the study protocol and informed written consent for genetic studies were approved by the Ethical and Research Committees of the Instituto Nacional de Geriatría of Mexico City, and the study was performed according to the ethical guidelines of the Declaration of Helsinki.

Statement of human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all the individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pérez-Suárez, T.G., Gutiérrez-Robledo, L.M., Ávila-Funes, J.A. et al. VNTR polymorphisms of the IL-4 and IL-1RN genes and their relationship with frailty syndrome in Mexican community-dwelling elderly. Aging Clin Exp Res 28, 823–832 (2016). https://doi.org/10.1007/s40520-015-0503-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40520-015-0503-4

Keywords

Navigation