Polymorphisms in the interleukin-4 and interleukin-4 receptor α chain genes confer susceptibility to asthma and atopy in a Caucasian population
Beghé, B., Barton, S., Rorke, S., Peng, Q., Sayers, I., Gaunt, T., Keith, T.P., Clough, J.B., Holgate, S.T. and Holloway, J.W. (2003) Polymorphisms in the interleukin-4 and interleukin-4 receptor α chain genes confer susceptibility to asthma and atopy in a Caucasian population. Clinical and Experimental Allergy, 33, (8), 1111-1117. (doi:10.1046/j.1365-2222.2003.01731.x).
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Background: IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype.
Objective: To investigate the role of four common polymorphisms in the IL-4 (IL4-34CT and IL4-589CT) and IL-4Rα chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma.
Methods: Two polymorphisms in the IL-4 gene promoter, IL4-34CT and IL4-589CT, and two polymorphisms in the IL-4Rα chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR-based methods in 341 asthmatic families and in 184 non-asthmatic adults recruited from the south of England.
Results: Case–control analysis did not reveal differences in the distribution of the four polymorphisms between asthmatics and controls. However, the transmission disequilibrium test showed that the IL4-589 T allele was preferentially transmitted to asthmatic children (P=0.036) and that the IL4RAQ576 was preferentially transmitted to children with atopic asthma (P=0.018). Haplotype analysis showed a strong association between the IL4-34T/-589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006).
Conclusion: Our data suggest that polymorphisms in the IL-4 and IL-4Rα chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.
|Keywords:||asthma, bronchial hyperresponsiveness, cytokines, genes, polymorphisms|
|Subjects:||H Social Sciences > HT Communities. Classes. Races
R Medicine > RB Pathology
Q Science > QH Natural history > QH426 Genetics
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
University Structure - Pre August 2011 > School of Medicine > Human Genetics
|Date Deposited:||25 Apr 2006|
|Last Modified:||02 Mar 2012 11:26|
|Contact Email Address:||J.W.Holloway@southampton.ac.uk|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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