STUDY OBJECTIVES: Pulmonary fibrosis develops in approximately 25% of patients with chronic sarcoidosis. Transforming growth factor (TGF)-beta1 plays a central role in fibrosis, and accruing reports address the implication of TGF-beta2 and TGF-beta3 in this process. We determined whether single-nucleotide polymorphisms (SNPs) in the TGF-beta1, TGF-beta2, and TGF-beta3 genes might contribute to pulmonary fibrosis in sarcoidosis patients. SETTING: A hospital in the Netherlands. DESIGN: Five SNPs per TGF-beta gene were investigated. PATIENTS AND CONTROL SUBJECTS: Patients with either acute/self-remitting sarcoidosis (n = 50) and Löfgren syndrome (n = 46) or chronic disease with fibrosis (n = 24) and without fibrosis (n = 34) were assessed over a 4-year follow-up period. The control subjects included 315 individuals. MEASUREMENTS AND RESULTS: Polymorphism frequencies were not discordant between the patients and control subjects. The TGF-beta3 4875 A allele was significantly higher in fibrotic patients (carrier frequency, 0.29) than in patients with acute/self-remitting (0.06) and chronic (0.03) sarcoidosis combined (corrected p = 0.01; odds ratio [OR], 7.9). The TGF-beta3 17369 C allele carrier frequency was significantly higher in fibrotic patients (0.29) compared to acute/self-remitting (0.08) and chronic (0.06) patients combined (corrected p = 0.05; OR, 5.1). Although not significant after correction, the TGF-beta3 15101 G allele carrier frequency was lower in fibrotic patients (0.79) compared to acute/self-remitting (0.94) and chronic (1.00) patients combined (p = 0.02; corrected p = 0.1; OR, 0.15). The TGF-beta2 59941 G allele was more abundant in fibrotic patients (carrier frequency, 0.62) compared to patients with acute/self-remitting (0.41) and chronic sarcoidosis combined (0.28) [p = 0.04; corrected p = 0.2; OR, 2.9]. TGF-beta1 gene polymorphisms were not associated with fibrosis. CONCLUSIONS: This study is the first to suggest the implication of genetic variation of TGF-beta3 in the predilection for pulmonary fibrosis developing in sarcoidosis patients.
STUDY OBJECTIVES:Pulmonary fibrosis develops in approximately 25% of patients with chronic sarcoidosis. Transforming growth factor (TGF)-beta1 plays a central role in fibrosis, and accruing reports address the implication of TGF-beta2 and TGF-beta3 in this process. We determined whether single-nucleotide polymorphisms (SNPs) in the TGF-beta1, TGF-beta2, and TGF-beta3 genes might contribute to pulmonary fibrosis in sarcoidosispatients. SETTING: A hospital in the Netherlands. DESIGN: Five SNPs per TGF-beta gene were investigated. PATIENTS AND CONTROL SUBJECTS:Patients with either acute/self-remitting sarcoidosis (n = 50) and Löfgren syndrome (n = 46) or chronic disease with fibrosis (n = 24) and without fibrosis (n = 34) were assessed over a 4-year follow-up period. The control subjects included 315 individuals. MEASUREMENTS AND RESULTS: Polymorphism frequencies were not discordant between the patients and control subjects. The TGF-beta3 4875 A allele was significantly higher in fibrotic patients (carrier frequency, 0.29) than in patients with acute/self-remitting (0.06) and chronic (0.03) sarcoidosis combined (corrected p = 0.01; odds ratio [OR], 7.9). The TGF-beta3 17369 C allele carrier frequency was significantly higher in fibrotic patients (0.29) compared to acute/self-remitting (0.08) and chronic (0.06) patients combined (corrected p = 0.05; OR, 5.1). Although not significant after correction, the TGF-beta3 15101 G allele carrier frequency was lower in fibrotic patients (0.79) compared to acute/self-remitting (0.94) and chronic (1.00) patients combined (p = 0.02; corrected p = 0.1; OR, 0.15). The TGF-beta2 59941 G allele was more abundant in fibrotic patients (carrier frequency, 0.62) compared to patients with acute/self-remitting (0.41) and chronic sarcoidosis combined (0.28) [p = 0.04; corrected p = 0.2; OR, 2.9]. TGF-beta1 gene polymorphisms were not associated with fibrosis. CONCLUSIONS: This study is the first to suggest the implication of genetic variation of TGF-beta3 in the predilection for pulmonary fibrosis developing in sarcoidosispatients.
Authors: Douglas G Mack; Allison M Lanham; Michael T Falta; Brent E Palmer; Lisa A Maier; Andrew P Fontenot Journal: Am J Respir Crit Care Med Date: 2010-03-18 Impact factor: 21.405
Authors: Bradford E Hall; Umesh D Wankhade; Joanne E Konkel; Karthik Cherukuri; Chandrasekharam N Nagineni; Kathleen C Flanders; Praveen R Arany; Wanjun Chen; Sushil G Rane; Ashok B Kulkarni Journal: J Biol Chem Date: 2013-09-20 Impact factor: 5.157
Authors: Elliott D Crouser; Mark W Julian; Melissa Crawford; Guohong Shao; Lianbo Yu; Stephen R Planck; James T Rosenbaum; S Patrick Nana-Sinkam Journal: Biochem Biophys Res Commun Date: 2011-12-24 Impact factor: 3.575
Authors: Karen C Patterson; Beverly S Franek; Joachim Müller-Quernheim; Anne I Sperling; Nadera J Sweiss; Timothy B Niewold Journal: Cytokine Date: 2013-02-04 Impact factor: 3.861