The relationship between MUC5B promoter, TERT polymorphisms and telomere lengths with radiographic extent and survival in a Chinese IPF cohort

Abstract

Genetic factors were identified to be associated with the development of idiopathic pulmonary fibrosis (IPF). We aimed to investigate associations between mucin 5B ( MUC5B) and telomerase reverse transcriptase ( TERT) polymorphisms and telomere length (TL) with honeycombing extent and survival in a Chinese IPF cohort. Seventy-nine patients diagnosed with IPF were enrolled. The honeycombing extents in high resolution CT scan (HRCT) were quantitatively scored and defined as mild (<10%), moderate (10–50%), and severe (>50%) upon the honeycombing extents involving the total lung. We tested five single-nucleotide polymorphisms [rs35705950, rs868903 in MUC5B, rs2736100, rs2853676 in TERT and rs1881984 in Telomerase RNA Gene ( TERC) and TLs in peripheral blood leucocytes, and evaluated their associations with radiographic extent and survival in IPF. The minor allele frequencies (MAF) were significantly greater for MUC5B rs868903 (P = 0.042) and TERT rs2853676 (P = 0.041) in IPF than those in healthy controls. CT/CC genotype of MUC5B rs868903 (p = 0.045) and short TLs (p = 0.035) were correlated with the more extensive honeycombing opacities in HRCT. After adjustment for age, sex, and smoking status, MUC5B rs868903 polymorphism was the significant gene risk factors for reduced survival (p = 0.044) in IPF. MUC5B promoter rs868903 polymorphism and TLs were associated with radiographic extent and survival in a Chinese IPF cohort. These findings suggested a genetic clue for exploring the underlying molecular basis and pathogenesis of IPF.