Transforming growth factor beta-1 gene polymorphisms and course of asthma

Abstract

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.