Premium
Mutation screening of interferon regulatory factor 1 gene (IRF‐1) as a candidate gene for atopy/asthma
Author(s) -
Noguchi E.,
Shibasaki M.,
Arinami T.,
YamakawaKobayashi K.,
Yokouchi Y.,
Takeda K.,
Matsui A.,
Hamaguchi H.
Publication year - 2000
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.2000.00916.x
Subject(s) - atopy , linkage disequilibrium , genetics , candidate gene , irf1 , biology , allele , immunology , asthma , gene , promoter , coding region , haplotype , gene expression
Background IL‐4 gene cluster on chromosome 5 contains several candidate genes for atopy and asthma. Several independent studies have shown evidence for linkage between the markers flanking IL‐4 gene cluster and asthma and/or asthma‐related traits. Interferon regulatory factor 1 (IRF‐1) is located approximately 300 kb telomeric to IL‐4 and recent study reveals that IRF‐1 deficiency results in an elevated production of Th2‐related cytokines and a compensatory decrease in the expression of native cell‐ and Th1‐related cytokines. Objective To determine if there are any mutations associated with the development of atopy and asthma present in the coding exons and 5′ flanking region of the IRF‐1 gene. Methods and results We have screened the promoter and coding regions of the IRF‐1 gene in atopic asthmatics and controls by SSCP method. We found three novel nuclear variants (the −300G/T and 4396 A/G polymorphisms and the 6355G > A rare variant) in the IRF‐1 gene. No variants causing amino acid alterations of IRF‐1 were detected. The −300G/T polymorphism was in nearly complete linkage disequilibrium with the 4396 A/G polymorphism. An association between the 4396 A > G polymorphism and atopy/asthma was examined by transmission disequilibrium test in 81 asthmatic families. Either of 4396 A or 4396G alleles was not significantly preferentially transmitted to atopy‐ or asthma‐affected children. Conclusion The IRF‐1 gene is less likely to play a substantial role in the development of atopy and asthma in the Japanese population.