The upregulation and SNP of Transforming growth factor-β1 in COPD patients with or without pulmonary fibrosis

Abstract

Background: Pulmonary fibrosis is a common pathogenic change of COPD and associated with worse outcome, however, there is a lack of research on mechanisms of COPD with pulmonary fibrosis. In our study, we studied the influence of TGF-β1 and its single nucleotide polymorphism (SNP) on COPD complicated with pulmonary fibrosis. Methods: In this research, six GEO datasets were included to screen dysregulated genes in COPD patients. The dysregulated genes were detected by PCR-DNA sequencing based on 98 COPD patients and 90 healthy volunteers. Results: Five genes were upregulated in COPD patients including CDCP1, CYP1B1, PELO, RNF24 and TGF-β1. However, of the five genes, only TGF-β and CYP1B1 expression were significantly increased in COPD compared with normal group validated by R2 database. And only TGF-β1 highly expressed in 1-4 stage of COPD versus 0 stage. The expression of TGF-β in COPD patients with fibrosis was significantly higher than normal and COPD patients. Moreover, allele C of TGF-β1 +869 locus was associated with the susceptibility of COPD and airflow restriction. The genotype frequency of CC in patients with severe airflow restriction (23.1%) was significantly higher than that in patients with mild and moderate airflow restriction (6.5%). Conclusion: TGF-β1 was upregulated in the COPD patients with fibrosis, especially in patients with pulmonary fibrosis. The SNP at +869 allele C in TGF-β1 may be a genetic locus and therapeutic target for COPD with fibrosis.