Role of IL-13 Genetic Variants in Signalling of Asthma

Inflammation. 2017 Apr;40(2):566-577. doi: 10.1007/s10753-016-0503-3.

Abstract

Asthma is a chronic inflammatory disease of the lower airways characterised by intermittent airway narrowing and airflow obstruction. The aim of this study was to examine the association of IL-13 Arg 130 Gln (A/G) and -1112C/T cytokine gene polymorphisms and to know the secretion of IL-13 cytokine levels and the interactions between the IL-13 130A/G and IL-13Rα1/IL-4Rα complex cytokine genes. The study population comprised of atopic and non-atopic asthma patients and healthy controls (HC) (N = 120). Single nucleotide polymorphisms (SNPs) were determined by restriction fragment length polymorphism (RFLP). IL-13 cytokine serum levels were measured by enzyme-linked immunosorbent assay (ELISA), and homology modelling of IL-13 A/G cytokine gene was performed through in silico analysis. In IL-13 130A/G cytokine gene AG, GG genotypes (p < 0.0042, OR = 2.87, CI 1.46-5.65; OR = 1.92, CI 1.06-3.48) were found to be significant in atopic asthma patients vs HC. The mean IL-13 serum cytokine levels were found to be significantly high in atopic (38.48 ± 36.54) and non-atopic (36.05 ± 34.54) asthma patients whereas total serum IgE levels were significantly high at p < 0.0001 in atopic and low in non-atopic asthma patients at p < 0.003 compared to HC. In silico analysis indicated that residue IL-13 130 with charge modifying variants was crucial in ligand-receptor interactions. IL-13 cytokine serum levels were significantly high in atopic and non-atopic asthma patients compared to HC. The GG genotype of IL-13 130A/G cytokine gene might be involved in the induced production of total IgE and IL-13 cytokine serum levels suggesting IL-13 may be important in the signalling of asthma.

Keywords: association studies; cytokine serum levels; homology modelling; signalling in asthma; total serum IgE.

MeSH terms

  • Adult
  • Asthma / genetics*
  • Asthma / metabolism
  • Case-Control Studies
  • Female
  • Genotype
  • Humans
  • Hypersensitivity, Immediate / blood
  • Hypersensitivity, Immediate / genetics
  • Immunoglobulin E / blood
  • Interleukin-13 / blood
  • Interleukin-13 / genetics*
  • Interleukin-13 / physiology
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Signal Transduction

Substances

  • Interleukin-13
  • Immunoglobulin E