Journal
CLINICAL AND EXPERIMENTAL ALLERGY
Volume 33, Issue 8, Pages 1111-1117Publisher
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.1365-2222.2003.01731.x
Keywords
asthma; bronchial hyperresponsiveness; cytokines; genes; polymorphisms
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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-4Ralpha 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-4Ralpha 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-4Ralpha chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.
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