Decorin and TGF-beta1 polymorphisms and development of COPD in a general population.
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.


CONCLUSIONS
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.
van Diemen
Cleo C
CC
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. c.c.van.diemen@med.umcg.nl
Postma
Dirkje S
DS
Vonk
Judith M
JM
Bruinenberg
Marcel
M
Nolte
Ilja M
IM
Boezen
H Marike
HM
D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005541:Forced Expiratory Volume / Q000502:physiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008957:Models, Genetic; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011509:Proteoglycans / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1