<it>Decorin </it>and <it>TGF-β</it>_{<it>1 </it>}polymorphisms and development of COPD in a general population

• Main Authors: Nolte Ilja M, Bruinenberg Marcel, Vonk Judith M, Postma Dirkje S, van Diemen Cleo C, Boezen H Marike
• Format: Article
• Language: English
• Published: BMC 2006-06-01
• Series: Respiratory Research
• Online Access: http://respiratory-research.com/content/7/1/89

<p>Abstract</p> <p>Background</p> <p>Decorin, an extracellular matrix (ECM) proteoglycan, and <it>TGF-β</it>_{<it>1 </it>}are both involved in lung ECM turnover. Decorin and <it>TGF-β</it>_{<it>1 </it>}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 <it>decorin </it>and <it>TGF-β</it>_{<it>1 </it>}underlie accelerated decline in FEV_{<it>1 </it>}and development of COPD in the general population.</p> <p>Methods</p> <p>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 <it>decorin </it>(3'UTR and four intron SNPs) and three SNPs in <it>TGF-β</it>_{<it>1 </it>}(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 FEV₁decline.</p> <p>Results</p> <p>We found a significantly higher prevalence of carriers of the minor allele of the <it>TGF-β</it>_{<it>1 </it>}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 <it>TGF-β</it>_{<it>1 </it>}in subjects with COPD (p = 0.030), indicating that this association is due to the rs6957 SNP. <it>TGF-β</it>_{<it>1 </it>}SNPs were not associated with FEV₁decline. SNPs in <it>decorin</it>, and haplotypes constructed of both <it>TGF-β</it>_{<it>1 </it>}and <it>decorin </it>SNPs were not associated with development of COPD or with FEV₁decline.</p> <p>Conclusion</p> <p>Our study shows for the first time that SNPs in <it>decorin </it>on its own or in interaction with SNPs in <it>TGF-β</it>_{<it>1 </it>}do not underlie the disturbed balance in expression between these genes in COPD. <it>TGF-β</it>_{<it>1 </it>}SNPs are associated with COPD, yet not with accelerated FEV₁decline in the general population.</p>