Polymorphisms in the interleukin‐4 and interleukin‐4 receptor α chain genes confer susceptibility to asthma and atopy in a Caucasian population
- 5 August 2003
- journal article
- research article
- Published by Wiley in Clinical and Experimental Allergy
- Vol. 33 (8), 1111-1117
- https://doi.org/10.1046/j.1365-2222.2003.01731.x
Abstract
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
This publication has 27 references indexed in Scilit:
- Allelic association and functional studies of promoter polymorphism in the leukotriene C4 synthase gene (LTC4S) in asthmaThorax, 2003
- Association of the ADAM33 gene with asthma and bronchial hyperresponsivenessNature, 2002
- Factor analysis of asthma and atopy traits shows 2 major components, one of which is linked to markers on chromosome 5qJournal of Allergy and Clinical Immunology, 2001
- A Second-Generation Association Study of the 5q31 Cytokine Gene Cluster and the Interleukin-4 Receptor in AsthmaGenomics, 2001
- Invited Lecture: Activation of the Epithelial Mesenchymal Trophic Unit in the Pathogenesis of AsthmaInternational Archives of Allergy and Immunology, 2001
- A Second‐Generation Genomewide Screen for Asthma‐Susceptibility Alleles in a Founder PopulationAmerican Journal of Human Genetics, 2000
- The genetic basis of atopic asthmaClinical and Experimental Allergy, 1999
- Linkage and allelic association of atopy and markers flanking the IL4‐receptor geneClinical and Experimental Allergy, 1998
- Common Polymorphisms in the Coding Part of the IL4-Receptor GeneBiochemical and Biophysical Research Communications, 1997
- The interleukin-4 receptor gene (IL4R) maps to 16p11.2–16p12.1 in human and to the distal region of mouse chromosome 7Genomics, 1991