Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University of Bucheon Hospital, Gyeonggi Do, Korea.
Hum Immunol. 2010 Nov;71(11):1147-53. doi: 10.1016/j.humimm.2010.07.002. Epub 2010 Jul 29.
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.
核因子-κB（NF-κB）调控着哮喘中气道炎症和重塑相关基因的表达。IKBA 可对 NF-κB 的活性进行严格调控，而 IKBA 基因的遗传多态性可能会对其产生影响。我们在韩国人群中研究了 IKBA 基因多态性与哮喘易感性之间的关系。在 BA（支气管哮喘）和 NC（正常对照）中进行基因分型。分别采用逆转录-聚合酶链反应（RT-PCR）、酶联免疫吸附试验（ELISA）和荧光素酶报告基因检测进行检测。-673A>T（rs2233407）与特应性哮喘患者的哮喘发病相关（比值比=0.56，p=0.004）。与 AA 基因型相比，具有 rs2233407 TT 基因型的 B 细胞系中 IKBA mRNA 水平更高（p=0.024）。与 A 基因型相比，rs2233407 T 基因型的荧光素酶活性更高（p=0.002）。与 AA 基因型相比，具有 rs2233407 TT 基因型的 B 细胞系中的总 IKBA 和 IKBA[p-S32]的细胞质水平更高（p=0.016 和 p=0.036），而细胞内的核 NF-κB 活性在具有 IKBA rs2233407 AA 基因型的细胞中比在具有 AA 基因型的细胞中更高（p=0.038）。IKBA rs2233407 A>T 多态性可能通过调节 IKBA 基因的转录水平而使个体易患特应性哮喘。
