Decorin, an extracellular matrix (ECM) proteoglycan, and TGF-β ₁ are both involved in lung ECM turnover. Decorin and TGF-β ₁ expression are decreased respectively increased in COPD lung tissue. Interestingly, they act as each other's feedback regulator. We investigated whether single nucleotide polymorphisms (SNPs) in decorin and TGF-β ₁ underlie accelerated decline in FEV ₁ and development of COPD in the general population.

We genotyped 1390 subjects from the Vlagtwedde/Vlaardingen cohort. Lung function was measured every 3 years for a period of 25 years. We tested whether five SNPs in decorin (3'UTR and four intron SNPs) and three SNPs in TGF-β ₁ (3'UTR rs6957, C-509T rs1800469 and Leu10Pro rs1982073), and their haplotypes, were associated with COPD (last survey GOLD stage = II). Linear mixed effects models were used to analyze genotype associations with FEV₁ decline.

We found a significantly higher prevalence of carriers of the minor allele of the TGF-β ₁ rs6957 SNP (p = 0.001) in subjects with COPD. Additionally, we found a significantly lower prevalence of the haplotype with the major allele of rs6957 and minor alleles for rs1800469 and rs1982073 SNPs in TGF-β ₁ in subjects with COPD (p = 0.030), indicating that this association is due to the rs6957 SNP. TGF-β ₁ SNPs were not associated with FEV₁ decline. SNPs in decorin, and haplotypes constructed of both TGF-β ₁ and decorin SNPs were not associated with development of COPD or with FEV₁ decline.

Our study shows for the first time that SNPs in decorin on its own or in interaction with SNPs in TGF-β ₁ do not underlie the disturbed balance in expression between these genes in COPD. TGF-β ₁ SNPs are associated with COPD, yet not with accelerated FEV₁ decline in the general population.