Interleukin (IL)-13 plays a central role in
asthma pathogenesis by binding to the
IL-13 receptor, which is a heterodimer composed of the
IL-13 receptor alpha1 subunit (IL-13Ralpha1) and IL-4Ralpha. The genetic diversity at the
IL-13Ralpha1 gene (IL13RA1) locus on chromosome Xq24 was characterised and the association of identified polymorphisms with
asthma and atopy phenotypes examined. The promoter and coding region of IL13RA1 were screened for common genetic variants, and polymorphisms found were genotyped in a large cohort of 341 asthmatic Caucasian families (each containing at least two asthmatic siblings) and 182 nonasthmatic control subjects. Genetic association was determined using case-control and transmission disequilibrium test analyses. Two common polymorphisms were identified, a newly found
thymidine (T) to
guanine (G) transition of
nucleotide -281 (-281T>G) single nucleotide polymorphism in the IL13RA1 promoter and the previously described 1365A>G variant in the IL13RA1 proximal
3' untranslated region. 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 the IL13RA1 -281T/1365A haplotype and raised total serum
immunoglobulin E levels in adult female asthmatics. These findings indicate that the
interleukin-13 receptor alpha1 subunit gene -281T>G and 1365A>G polymorphisms do not contribute to
asthma susceptibility or severity, although the
interleukin-13 receptor alpha1 subunit gene locus might be involved in the control of
immunoglobulin E production.