Role of IL-13 Genetic Variants in Signalling of Asthma
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ORIGINAL ARTICLE
Role of IL-13 Genetic Variants in Signalling of Asthma Madhavi Latha Alasandagutti,1 Mohd Soheb Sadat Ansari,1 S. R. Sagurthi,2 Vijayalakshmi Valluri,3 and Sumanlatha Gaddam1,2,4
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 enzymelinked 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 nonatopic 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. KEY WORDS: association studies; total serum IgE; cytokine serum levels; homology modelling; signalling in asthma.
INTRODUCTION Asthma is one of the most common disorders encountered in both children and adults characterised by airway obstruction, bronchohyperresponsiveness (BHR) and airway inflammation. This is orchestrated and regulated Electronic supplementary material The online version of this article (doi:10.1007/s10753-016-0503-3) contains supplementary material, which is available to authorized users. 1
Bhagwan Mahavir Medical Research Centre, Hyderabad, Telangana 500004, India 2 Osmania University, Hyderabad, Telangana 500007, India 3 LEPRA India—Blue Peter Public Health & Research Centre, Cherlapally, Hyderabad, Telangana 501301, India 4 To whom correspondence should be addressed at Osmania University, Hyderabad, Telangana 500007, India. E-mail: [email protected]
majorly by a complex network of mutually interacting cytokines. The Th2 cytokines in relation to asthma mainly focussed on IL-4 and IL-13 as they play a crucial role in generating Th2 responses. IL-4 cytokine is thought to be B cell growth factor. It promotes the development of TH2
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