RT Journal Article
SR Electronic
T1 Genetic association studies of interleukin-13 receptor α1 subunit gene polymorphisms in asthma and atopy
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 40
OP 47
DO 10.1183/09031936.00025706
VO 30
IS 1
A1 A. K. Konstantinidis
A1 S. J. Barton
A1 I. Sayers
A1 I. A. Yang
A1 J. L. Lordan
A1 S. Rorke
A1 J. B. Clough
A1 S. T. Holgate
A1 J. W. Holloway
YR 2007
UL http://erj.ersjournals.com/content/30/1/40.abstract
AB 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 α1 subunit (IL-13Rα1) and IL-4Rα. The genetic diversity at the IL-13Rα1 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 α1 subunit gene -281T>G and 1365A>G polymorphisms do not contribute to asthma susceptibility or severity, although the interleukin-13 receptor α1 subunit gene locus might be involved in the control of immunoglobulin E production.