Decorin and TGF-β1 polymorphisms and development of COPD in a general population
نویسندگان
چکیده
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.
منابع مشابه
Anti-inflammatory effect of Yu-Ping-Feng-San via TGF-β1 signaling suppression in rat model of COPD
Objective(s): Yu-Ping-Feng-San (YPFS) is a classical traditional Chinese medicine that is widely used for treatment of the diseases in respiratory systems, including chronic obstructive pulmonary disease (COPD) recognized as chronic inflammatory disease. However, the molecular mechanism remains unclear. Here we detected the factors involved in transforming growth factor beta 1 (TGF-β1)/Smad2 si...
متن کاملGenotype-phenotype association of TGF-β1 and GST with chemo-radiotherapy induced toxicity
Background: Normal tissue toxicity continues to remain as a major challenge for radiation oncologists for delivering the total dose to the tumour cells in cancer patients. Cellular, molecular and plasma based early biomarkers to predict the overreactions and non-overreactions of normal tissue toxicity before the initiation of radiotherapy can be valuable for personalised treatment. The aim of t...
متن کاملFOXP3 and TGF-β Gene Polymorphisms in Allergic Rhinitis
Background: Regulatory CD4+T (Treg) cells are effective in maintaining immune tolerance. Objective: To investigate single nucleotide polymorphisms (SNPs) of Transforming Growth Factor β-1 (TGF-β1) and Forkhead Box Protein 3 (FOXP3) genes in Iranian patients with allergic rhinitis (AR). Methods: Variations at codons 10 and 25 of TGF-β1 and FOXP3 at positions -3279 A>C and -924 A>G were evaluated...
متن کاملبررسی همبستگی بین پلی مورفیسم G>C 915 ژن TGF-B1با عفونت مزمن هپاتیتC
Background & Objective: Cytokines are immune system factors known to play a key role in both HCV clearance and the development of infection the impact of host genetic factors on the clinical outcome of HCV infection has not been elucidated. On the other hand, the impact of Genetic changes like Single nucleotide polymorphisms on expression rate and function of Cytokine is under study. The aim ...
متن کاملProtective effects of eight weeks interval aerobic exercise on decorin, TGF-β and tumor volume in atypical animal of breast cancer
Introduction: The decorin is a myokine that modulates the growth and the development of the cancer cells through the interaction with TGF-β. The present study is aimed to evaluate the protective effects of 8 weeks interval aerobic exercise on the expression of decorin and TGF-β, and tumor volume in a typical animal of breast tumor. Materials and Methods: In a exprimental research, forty adult f...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Respiratory Research
دوره 7 شماره
صفحات -
تاریخ انتشار 2006