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Association of IκB‐α of polymorphism with development of asthma
Author(s) -
Park SeMin,
Chang HunSoo,
Park ChoonSik,
Rhim Tae Youn,
Jang AnSoo,
Lee MiYoung,
Park Byung Lae,
Uh SooTaek,
Shin Hyoung Doo,
Chung Il Yup
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.798.3
Subject(s) - single nucleotide polymorphism , snp , allele , luciferase , microbiology and biotechnology , christian ministry , population , genetics , biology , promoter , gene , genotype , medicine , gene expression , transfection , philosophy , theology , environmental health
The development of asthma is determined by the interaction between host susceptibility and a variety of environmental exposures. NF‐κ B activates many immunoregulatory genes. The I κB‐α is an endogenous inhibitor of NF‐ κB. This study examined the association between I κB‐ α gene polymorphisms and susceptibility to asthma. The SNPs were genotyped by single base extension method in Korean population. RT‐PCR and luciferase reporter assay were performed. Iκ B‐α activity was evaluated with EMSA. One novel SNP (+3075 G>A) was discovered, and the five reported SNPs were found in the Korean population. The frequency of rare allele (−689 A>T) was significantly lower in asthmatics than normal controls (OR = 0.516, p=0.037), especially in atopic subject (p=0.007). The mRNA level was significantly higher in B cell lines of I κB‐α −689 TT type than those of AA type (p=0.024). The luciferase activity of c.‐689 T type of I κB‐α promoter was significantly higher than that of A type (p= 0.002). A nuclear protein showed stronger DNA binding affinity with a probe containing c.‐689 A than that of T. Our data suggest that the I κB‐α −689 A>T SNP participates in the regulation of I κB‐α expression by providing a potential binding site for a repressor, and that the I κB‐α −689 A>T SNP may predict asthma phenotypes. Funded By: the Korea health 21 R&D project. Ministry of Health & Welfare. Republic of Korea (01‐PJ3‐PG6‐01GN04‐0003).