title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  The IRF-1 gene is less likely to play a substantial role in the development of atopy and asthma in the Japanese population.
authors.affiliation: Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Noguchi
authors.forename: M
authors.initials: M
authors.lastname: Shibasaki
authors.forename: T
authors.initials: T
authors.lastname: Arinami
authors.forename: K
authors.initials: K
authors.lastname: Yamakawa-Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Yokouchi
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: A
authors.initials: A
authors.lastname: Matsui
authors.forename: H
authors.initials: H
authors.lastname: Hamaguchi
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D050856:Interferon Regulatory Factor-1; D015847:Interleukin-4 / Q000235:genetics; D015810:Linkage Disequilibrium; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D015847:Interleukin-4