RT Journal Article
SR Electronic
T1 Transforming growth factor beta-1 gene polymorphisms and course of asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 3229
VO 38
IS Suppl 55
A1 Despo Ierodiakonou
A1 Dirkje S. Postma
A1 Gerard H. Koppelman
A1 Jorrit Gerritsen
A1 Wim Timens
A1 H. Marike Boezen
A1 Judith M. Vonk
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/3229.abstract
AB TGFβ1 is a cytokine with a potent role in asthma, in particular in airway remodeling. We investigated the role of TGFβ1 gene single nucleotide polymorphisms (SNPs) in the course of asthma.Four haplotype tagging SNPs (rs7254679, rs4803455, rs1800469, rs10417924) were genotyped in 215 asthmatics with a 30-year follow up (population 1) and in 99 asthmatics who provided bronchial biopsies (population 2). Associations of SNPs with lung function, bronchial hyperresponsiveness (BHR i.e. PC20≤16mg/ml), complete remission (pre bronchodilation FEV1% predicted ≥ 80% & absence of BHR, symptoms, medication), basement membrane (BM) thickness and number of submucosal vessels were investigated using linear or logistic regression. Associations of SNPs with FEV1 decline were estimated using mixed effect models, and associations with area covered with smooth muscle and collagen were tested non parametrically.Population 1: the G-allele of rs7254679 was associated with lower FEV1 (b (95%CI)=-21.2ml (-40.8;-2.0) and VC (b=-29.8ml (-49.3;-10.4)), increased risk for BHR (OR (95%CI)=2.7 (1.02-6.5)) and less remission (OR=0.3 (0.09-0.99)) The A-allele of rs4803455 was associated with accelerated FEV1 decline (b=-13.8ml/year (-20.9;-6.7)) and the T-allele of rs1800469 with less FEV1 decline (b=7.2ml/year (0.8;13.7). Population 2: the G-allele of rs7254679 tended to be associated with increased BM thickness (b=0.7 (-0.1;1.4 p=0.09)).This is the first study indicating that TGFβ1 SNPs play a role in the course of asthma. Further analysis of data of another 40 subjects with bronchial biopsies will allow us to investigate the associations between TGFβ1 SNPs and airway remodeling in asthma in more detail.