Science and Research

IRF-1 SNPs influence the risk for childhood allergic asthma: A critical role for pro-inflammatory immune regulation

BACKGROUND: Allergic and non-allergic childhood asthma has been characterized by distinct immune mechanisms. While interferon regulating factor 1 (IRF-1) polymorphisms (SNPs) influence atopy risk, the effect of SNPs on asthma phenotype-specific immune mechanisms is unclear. We assessed whether IRF-1 SNPs modify distinct immune-regulatory pathways in allergic and non-allergic childhood asthma (AA/NA). METHODS: In the CLARA study, asthma was characterized by doctor's diagnosis and AA vs NA by positive or negative specific IgE. Children were genotyped for four tagging SNPs within IRF-1 (n = 172). mRNA expression was measured with qRT-PCR. Gene expression was analyzed depending on genetic variants within IRF-1 and phenotype including haplotype estimation and an allelic risk score. RESULTS: Carrying the risk alleles of IRF-1 in rs10035166, rs2706384, or rs2070721 was associated with increased risk for AA. Carrying the non-risk allele in rs17622656 was associated with lower risk for AA but not NA. In AA carrying the risk alleles, an increased pro-inflammatory expression of ICAM3, IRF-8, XBP-1, IFN-gamma, RGS13, RORC, and TSC2 was observed. NOD2 expression was decreased in AA with risk alleles in rs2706384 and rs10035166 and with risk haplotype. Further, AA with risk haplotype showed increased IL-13 secretion. NA with risk allele in rs2070721 compared to non-risk allele in rs17622656 showed significantly upregulated calcium, innate, mTOR, neutrophil, and inflammatory-associated genes. CONCLUSION: IRF-1 polymorphisms influence the risk for childhood allergic asthma being associated with increased pro-inflammatory gene regulation. Thus, it is critical to implement IRF-1 genetics in immune assessment for childhood asthma phenotypes.

  • Landgraf-Rauf, K.
  • Boeck, A.
  • Siemens, D.
  • Klucker, E.
  • Vogelsang, V.
  • Schmidt, S.
  • Kunze, S.
  • Weissenbacher, C.
  • Graessel, A.
  • Schmidt-Weber, C.
  • von Mutius, E.
  • Schedel, M.
  • Schaub, B.

Keywords

  • Adolescent
  • Asthma/*genetics
  • Child
  • Child, Preschool
  • Cytokines/metabolism
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Immunoglobulin E/blood
  • Interferon Regulatory Factor-1/*genetics
  • Polymorphism, Single Nucleotide
  • Real-Time Polymerase Chain Reaction
  • Respiratory Function Tests/methods
  • Risk
  • *Ca-signaling
  • *irf-1
  • *asthma
  • *childhood
  • *pro-inflammatory
  • *single nucleotide polymorphism
Publication details
DOI: 10.1111/pai.12821
Journal: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
Pages: 34-41 
Number: 1
Work Type: Original
Location: CPC-M
Disease Area: AA
Partner / Member: LMU
Access-Number: 29047170
See publication on PubMed

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