Association of IKBA gene polymorphisms with the development of asthma.
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.
Park
Se-Min
SM
Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University of Bucheon Hospital, Gyeonggi Do, Korea.
Chang
Hun-Soo
HS
Rhim
Taiyoun
T
Park
Sung Woo
SW
Jang
An Soo
AS
Park
Jong Sook
JS
Uh
Soo-Taek
ST
Na
Ju Ock
JO
Hwang
Hun-Gyu
HG
Kim
Yong Hoon
YH
Lee
Mi Young
MY
Chung
Il Yup
IY
Park
Byung Lae
BL
Shin
Hyung Doo
HD
Park
Choon-Sik
CS
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
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha