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. 2016 Oct;28(5):823-32. doi: 10.1007/s40520-015-0503-4. Epub 2015 Dec 8.

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 (low) -IL-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 (low) -IL-1Ra (high) genotype might be genetic markers of susceptibility to frailty in Mexican elderly.

Keywords: Frailty; Genetic susceptibility; IL-1RN; IL-4; Older adults; VNTR polymorphism.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Disability Evaluation
  • Female
  • Frail Elderly / statistics & numerical data*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genotype
  • Geriatric Assessment / methods
  • Humans
  • Independent Living / statistics & numerical data
  • Interleukin 1 Receptor Antagonist Protein / genetics*
  • Interleukin-4 / genetics*
  • Male
  • Mexico / epidemiology
  • Minisatellite Repeats / genetics*
  • Polymorphism, Genetic

Substances

  • Genetic Markers
  • IL1RN protein, human
  • IL4 protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-4