A novel approach to understanding the role of polymorphic forms of the NR3C1 and TGF-beta 1 genes in the modulation of the expression of IL-5 and IL-15 mRNA in asthmatic inflammation

摘要

The aim of the present study was to identify polymorphic forms of the nuclear receptor subfamily 3, group C, member 1 (NR3C1) and transforming growth factor 1 (TGF-1) genes and evaluate their impact on the expression levels of interleukin (IL)-5 and IL-15 in asthma. The study was conducted on a control group consisting of 91 people (54 women and 37 men). The patient group consisted of 130 participants (86 women and 44 men). Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR-high resolution melting (HRM) methods. Interleukin expression was measured by reverse transcription-quantitative polymerase chain reaction. The frequency of the polymorphic forms in the analyzed group were observed to be: Tth111I (rs10052957) controls AA 0.0440, AG 0. 5714, GG 0.3846, patients AA 0.1538/AG 0.4692, GG 0.3769; ER22/23EK (rs6189/rs6190) controls AG 0.0556, GG 0.9444, patients AG 0.0385, GG 0.9615; N363S (rs6195) controls AA 0.6444, AG 0.2667, GG 0.0889, patients AA 0.7846, AG 0.1385, GG 0.0769; BclI (rs41423247) controls CC 0.0879, CG 0.5604, GG 0.3516, patients CC 0.1008, CG 0.5736, GG 0.3256; C-509T (rs1800469) controls TT 0.0805, CT 0.6322, CC 0.2874, patients TT 0.1102, CT 0.5669, CC 0.3228. The results indicated that the C-509T single nucleotide polymorphism (SNP) of the TGF-1 gene contributed to an increase in the IL-5 mRNA expression levels. The GG genotype of the N363S SNP of the NR3C1 gene was observed to result in an increase in the expression levels of IL-15. The present study indicated that the selected SNPs of the NR3C1 and TGF-1 genes demonstrate a regulatory effect on the expression of IL-5 and IL-15. Therefore, genetic variation affects inflammation in asthma and the clinical course of the disease.