Mutation screening of interferon regulatory factor 1 gene (IRF-1) as a candidate gene for atopy/asthma.

Abstract

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.

• Authors: E Noguchi, M Shibasaki, T Arinami, K Yamakawa-Kobayashi, Y Yokouchi, K Takeda, A Matsui, H Hamaguchi
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 30 Issue 11 Pg. 1562-7 (Nov 2000) ISSN: 0954-7894 [Print] England
• PMID: 11069564 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• IRF1 protein, human
• Interferon Regulatory Factor-1
• Phosphoproteins
• Interleukin-4

Topics

• Adolescent
• Adult
• Asthma (genetics)
• Child
• Child, Preschool
• DNA-Binding Proteins (genetics)
• Exons
• Humans
• Hypersensitivity, Immediate (genetics)
• Interferon Regulatory Factor-1
• Interleukin-4 (genetics)
• Linkage Disequilibrium
• Mutation
• Phosphoproteins (genetics)
• Polymorphism, Single Nucleotide
• Promoter Regions, Genetic