TGFβ1 allele association with asthma severity
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- Pulleyn, L.J., Newton, R., Adcock, I.M. et al. Hum Genet (2001) 109: 623. doi:10.1007/s00439-001-0617-y
Transforming growth factor β1 (TGFβ1) is a multifunctional cytokine involved in pro- and anti-inflammatory pathways and is expressed in several cell types. Subepithelial fibrosis is one of the principle features of airway remodelling in asthma and is increased in severe patients. TGFβ1 is implicated in fibrosis, including the deposition of extracellular matrix proteins. TGFβ1 mRNA levels in eosinophils are increased in severe asthmatics relative to mild asthmatics. Therefore, TGFβ1 is a promising candidate gene for contributing to asthma severity. Four polymorphisms located in the promoter region and signal peptide (C–509T, 72insC, T869C and G915C) were genotyped in groups of severe asthmatic, mild asthmatic or control individuals defined by steroid usage and pulmonary function. Significant differences (P=0.016) were found between the groups for the genotype frequencies at C–509T, attributable mainly to a greater relative frequency of homozygosity for the –509T allele in the severe group compared to the mild and control groups. Individuals homozygous for –509T were also homozygous at the other variant sites for the 72C, 869C and 915G alleles (haplotype 1). The T allele creates a putative YY1 transcription factor binding site, but binding between YY1 and the DNA sequence of the T allele was not detected in vitro. In this study, we show that the –509T variant on haplotype 1 is the most informative marker of the TGFβ1 contribution to asthma severity.