Association of IKBA gene polymorphisms with the development of asthma

Abstract

Nuclear factor-κB (NF-κB) orchestrates the expression of genes responsible for airway inflammation and remodeling in asthma. The activity of NF-κB is tightly regulated by IKBA, which may be modulated by genetic polymorphisms of the IKBA gene. We investigated the association between asthma susceptibility and IKBA gene polymorphisms in a Korean population. Genotyping was performed in BA (bronchial asthma) and NC (normal control). We measured reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and luciferase reporter assays, respectively. A -673A>T (rs2233407) was associated with asthma development in subjects with atopic asthma (odds ratio = 0.56, p = 0.004). The IKBA mRNA level was higher in B-cell lines with the rs2233407 TT genotype compared with those with the AA genotype (p = 0.024). The luciferase activity of the rs2233407 T genotype was higher than that of the A (p = 0.002). The cytoplasmic levels of total IKBA and IKBA [p-S32] were higher in B cell lines of the rs2233407 TT genotype than those of the AA (p = 0.016 and p = 0.036, respectively), whereas nuclear NF-κB activity in cells with the IKBA rs2233407 AA genotype was higher than in cells with the AA (p = 0.038). The IKBA rs2233407 A>T polymorphism may predispose individuals to the development of atopic asthma via regulation of IKBA gene expression at the transcriptional level.