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Respiratory Research

, 7:89

First Online: 16 June 2006Received: 22 December 2005Accepted: 16 June 2006


BackgroundDecorin, an extracellular matrix ECM proteoglycan, and TGF-β1 are both involved in lung ECM turnover. Decorin and TGF-β1 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-β1 underlie accelerated decline in FEV1 and development of COPD in the general population.

MethodsWe 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-β1 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.

ResultsWe found a significantly higher prevalence of carriers of the minor allele of the TGF-β1 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-β1 in subjects with COPD p = 0.030, indicating that this association is due to the rs6957 SNP. TGF-β1 SNPs were not associated with FEV1 decline. SNPs in decorin, and haplotypes constructed of both TGF-β1 and decorin SNPs were not associated with development of COPD or with FEV1 decline.

ConclusionOur study shows for the first time that SNPs in decorin on its own or in interaction with SNPs in TGF-β1 do not underlie the disturbed balance in expression between these genes in COPD. TGF-β1 SNPs are associated with COPD, yet not with accelerated FEV1 decline in the general population.

Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-7-89 contains supplementary material, which is available to authorized users.

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Autor: Cleo C van Diemen - Dirkje S Postma - Judith M Vonk - Marcel Bruinenberg - Ilja M Nolte - H Marike Boezen


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