IL‑13 and FOXO3 genes polymorphisms regulate IgE levels in asthmatic patients

Abstract

Immunoglobulin E (IgE) serves a crucial role in the pathogenesis of several allergic disorders, and elevated levels of total serum IgE have been associated with asthma. IgE is responsible for the release of several asthma-associated inflammatory mediators from mast cells, such as histamine and prostaglandins. The aim of the present study was to assess the association of interleukin (IL)-13 single nucleotide polymorphism (SNP) rs20541 and forkhead box O3a (FOXO3a) SNP rs13217795 with IgE levels in asthmatic patients and a healthy control group. Genetic polymorphism analysis of SNPs was performed using PCR/restriction fragment length polymorphism. Total serum IgE levels were measured using an ELISA kit. Genotypes were grouped into three models: Co-dominant, dominant and recessive. Major and minor alleles for IL-13 SNP rs20541 and FOXO3a SNP rs13217795 were C and T, whereas for IL-13, they were G and A, respectively. There was a significant association between the IL-13 rs20541 SNP and the total IgE serum levels, in which pure minor alleles were associated with a significant reduction (~5x lower) in IgE serum levels compared with the major alleles in asthmatic subjects and to a lesser extent in the control subjects. Additionally, the FOXO3a rs13217795 SNP was associated with a significant increase in total IgE levels (~5x higher) in the asthmatic patients compared with the control subjects. In conclusion, the present study confirmed that there was a significant association between the IL-13 SNP rs20541 and asthma, and an association between the FOXO3a SNP rs13217795 with asthma pathogenicity in Jordanian subjects.

Association of Interleukin 13 rs20541 Gene Polymorphism and Serum Periostin with Asthma and Allergic Conjunctivitis Among Egyptian Patients

“…This comes consistent with Imraish et al who reported a significant association between the homozygous (AA) genotype and asthmatic patients compared to control subjects (p = 0.0097). 40 The replacement of the G allele, the major allele, by the A allele, the minor one, in IL13 rs20514 has been shown previously to be associated with higher IL13 activity as it results in the replacement of the positively charged arginine by the neutral glutamine increasing the interaction between IL13 and its receptor IL4Rα/IL13Rα1. 46 The current study recorded a higher frequency of the minor A allele among asthmatics compared to healthy subjects (31.5% and 24.1%, respectively) yet with no significant difference (p 0.177).…”

“…This comes consistent with Imraish et al who reported a significant association between the homozygous (AA) genotype and asthmatic patients compared to control subjects (p = 0.0097). 40 …”

“…37,38 Several studies have reported the SNPs in the IL13 gene to be associated with susceptibility to allergic disorders and their severity. 7,[39][40][41][42] However, meta-analysis studies have shown that the frequencies of different SNPs and their contribution to allergic disorders vary among populations of different ethnicities. 43,44 The current work did not find a significant difference between allergic patients as a whole and control subjects regarding the genotype and allele distribution of IL13 rs20541 gene polymorphism.…”

The association between FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a among chronic granulocytic leukemia patients treated with imatinib mesylate

“…This possible mechanism was supported by a previous study. 20 The authors revealed that a dominant homozygote genotype of the FOXO3a rs4946936 gene variant was reported to associate with elevated levels of immunoglobulin (Ig) E in the case of asthma. They proposed that FOXO3a might regulate the production of proinflammatory cytokine, and cause elevated levels of IgE.…”

“…They proposed that FOXO3a might regulate the production of proinflammatory cytokine, and cause elevated levels of IgE. 20 Second, free energy levels between genotypes of the FOXO3a rs4946936 gene polymorphism might affect the levels of FOXO3a in the circulation. In an in silico study, the free energy levels of the CC and TT genotype of the FOXO3a rs4946936 gene variant were −320.80 Kcal/mol and −301.10 Kcal/mol, respectively, indicating that the CC genotype had lower free energy levels.…”