Genetic association studies of IL13RA1 polymorphisms in asthma and atopy

¹ Divisions of Human Genetics; and Infection, Inflammation and Repair, School of Medicine, University of Southampton, Southampton, UK
² Infection, Inflammation and Repair, School of Medicine, University of Southampton, Southampton, UK
³ Divisions of Human Genetics

^* To whom correspondence should be addressed. E-mail: a-konstantinidis{at}northwestern.edu.

	Abstract

IL-13 plays a central role in asthma pathogenesis by binding to the IL-13 receptor, which is a heterodimer composed of the IL-13R1 and the IL-4R subunits. We characterized the genetic diversity in the IL13RA1 locus on chromosome Xq24 and examined the association of identified polymorphisms with asthma and atopy phenotypes.

The promoter and the coding region of IL13RA1 were screened for common genetic variants, and polymorphisms found were genotyped in a large cohort of 341 asthmatic Caucasian families (containing at least two asthmatic siblings) and 182 non-asthmatic control subjects. Genetic association was determined using case control, genotype-phenotype, genotype-haplotype, and TDT analyses.

Two common polymorphisms were identified, a newly found -281T>G SNP in the IL13RA1 promoter, and the previously described 1365A>G variant in the IL13RA1 proximal 3' UTR. No significant association of either -281T>G or 1365A>G with risk of asthma or atopy phenotypes was found, apart from a suggestive association between IL13RA1 -281T/1365A haplotype and raised total serum IgE in adult female asthmatics.

These findings suggest that the IL13RA1 -281T>G and 1365A>G polymorphisms do not contribute to asthma susceptibility or severity, although the IL13RA1 locus might be involved in the control of IgE production.