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Decorin and TGF-beta1 polymorphisms and development of COPD in a general population
Cleo C van Diemen1, Dirkje S Postma, Judith M Vonk
1Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. c.c.van.diemen@med.umcg.nl
Background:
Decorin, an extracellular matrix (ECM) proteoglycan, and TGF-beta1 are both involved in lung ECM turnover. Decorin and TGF-beta1 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-beta1 underlie accelerated decline in FEV1 and development of COPD in the general population.
Methods:
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-beta1 (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.
Results:
We found a significantly higher prevalence of carriers of the minor allele of the TGF-beta1 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-beta1 in subjects with COPD (p = 0.030), indicating that this association is due to the rs6957 SNP. TGF-beta1 SNPs were not associated with FEV1 decline. SNPs in decorin, and haplotypes constructed of both TGF-beta1 and decorin SNPs were not associated with development of COPD or with FEV1 decline.
Conclusion:
Our study shows for the first time that SNPs in decorin on its own or in interaction with SNPs in TGF-beta1 do not underlie the disturbed balance in expression between these genes in COPD. TGF-beta1 SNPs are associated with COPD, yet not with accelerated FEV1 decline in the general population.
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