BACKGROUND: Several polymorphisms in the IL-4 receptor alpha (IL4RA) gene have been associated with asthma and atopy, but with variable success in different populations. Immunologic studies suggest that IL4RA may interact with other cytokines and receptors, and gene-gene interactions have also been observed with respect to asthma. Such interactions have been proposed to explain partly the difficulties in replicating association studies. METHODS: Using the prospective birth cohort BAMSE, we examined eight single nucleotide polymorphisms (SNPs) and corresponding haplotypes in the IL4RA gene in relation to wheezing and sensitization up to age 4. We also evaluated potential interaction effects (departure from a multiplicative interaction model) between the IL4RA SNPs and four SNPs in the IL-9 receptor (IL9R) gene previously associated with childhood wheezing. RESULTS: We found no main effect of the IL4RA SNPs alone and only weak associations to wheezing and sensitization when haplotypes were considered. Gene-gene interactions between several IL4RA and IL9R SNPs with regard to wheezing were observed (P=0.009), especially between IL4RA Q576R (rs1801275) and IL9R rs731476 (P=0.005). An interaction was also seen between IL4RA and IL9R haplotypes. CONCLUSION: Variants in the IL4RA gene alone may not exert any major influence on susceptibility to asthma-related diseases in childhood, but in combination with other genes, such as IL9R, IL4RA may be an important gene for disease susceptibility.
BACKGROUND: Several polymorphisms in the IL-4 receptor alpha (IL4RA) gene have been associated with asthma and atopy, but with variable success in different populations. Immunologic studies suggest that IL4RA may interact with other cytokines and receptors, and gene-gene interactions have also been observed with respect to asthma. Such interactions have been proposed to explain partly the difficulties in replicating association studies. METHODS: Using the prospective birth cohort BAMSE, we examined eight single nucleotide polymorphisms (SNPs) and corresponding haplotypes in the IL4RA gene in relation to wheezing and sensitization up to age 4. We also evaluated potential interaction effects (departure from a multiplicative interaction model) between the IL4RA SNPs and four SNPs in the IL-9 receptor (IL9R) gene previously associated with childhood wheezing. RESULTS: We found no main effect of the IL4RA SNPs alone and only weak associations to wheezing and sensitization when haplotypes were considered. Gene-gene interactions between several IL4RA and IL9R SNPs with regard to wheezing were observed (P=0.009), especially between IL4RAQ576R (rs1801275) and IL9Rrs731476 (P=0.005). An interaction was also seen between IL4RA and IL9R haplotypes. CONCLUSION: Variants in the IL4RA gene alone may not exert any major influence on susceptibility to asthma-related diseases in childhood, but in combination with other genes, such as IL9R, IL4RA may be an important gene for disease susceptibility.
Authors: Fred D Finkelman; Simon P Hogan; Gurjit K Khurana Hershey; Marc E Rothenberg; Marsha Wills-Karp Journal: J Immunol Date: 2010-02-15 Impact factor: 5.422
Authors: Samuel A Collins; Katharine C Pike; Hazel M Inskip; Keith M Godfrey; Graham Roberts; John W Holloway; Jane S A Lucas Journal: Pediatr Pulmonol Date: 2013-02-08
Authors: Nathalie Acevedo; Annika Sääf; Cilla Söderhäll; Erik Melén; Jami Mandelin; Christina Orsmark Pietras; Sini Ezer; Piia Karisola; Johanna Vendelin; Gustav Boije af Gennäs; Jari Yli-Kauhaluoma; Harri Alenius; Erika von Mutius; Gert Doekes; Charlotte Braun-Fahrländer; Josef Riedler; Marianne van Hage; Mauro D'Amato; Annika Scheynius; Göran Pershagen; Juha Kere; Ville Pulkkinen Journal: PLoS One Date: 2013-04-02 Impact factor: 3.240
Authors: Elizabeth E Forbes; Katherine Groschwitz; J Pablo Abonia; Eric B Brandt; Elizabeth Cohen; Carine Blanchard; Richard Ahrens; Luqman Seidu; Andrew McKenzie; Richard Strait; Fred D Finkelman; Paul S Foster; Klaus I Matthaei; Marc E Rothenberg; Simon P Hogan Journal: J Exp Med Date: 2008-03-31 Impact factor: 14.307