title: 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.
authors.affiliation: Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University of Bucheon Hospital, Gyeonggi Do, Korea.
authors.forename: Se-Min
authors.initials: SM
authors.lastname: Park
authors.forename: Hun-Soo
authors.initials: HS
authors.lastname: Chang
authors.forename: Taiyoun
authors.initials: T
authors.lastname: Rhim
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: An Soo
authors.initials: AS
authors.lastname: Jang
authors.forename: Jong Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Ju Ock
authors.initials: JO
authors.lastname: Na
authors.forename: Hun-Gyu
authors.initials: HG
authors.lastname: Hwang
authors.forename: Yong Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Il Yup
authors.initials: IY
authors.lastname: Chung
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Hyung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000328:Adult; D001249:Asthma / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D007723:Korea; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012129:Respiratory Function Tests
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha