Association Between Single Nucleotide Polymorphisms and Disease Susceptibility, Survival, and Acute Exacerbation in Idiopathic Pulmonary Fibrosis.

Background and objective: Genetic polymorphisms have been associated with susceptibility to interstitial lung diseases including idiopathic pulmonary fibrosis (IPF). We have now examined the relation between single nucleotide polymorphisms (SNPs) and clinical course, including acute exacerbation (AE), in addition to disease susceptibility for IPF and unclassifiable idiopathic interstitial pneumonias (IIPs).

Methods: DNA samples were collected from 223 IPF patients and 160 unclassifiable IIP patients included in a prospective, multicentre observational study in Japan. Nonfibrotic control subjects (n = 379) were selected from a previous study. Genotyping of TERT rs2736100, TERC rs1881984, MUC5B rs35705950, DSP rs2076295, and AKAP13 rs62025270 was conducted with commercial assays. The association between these SNPs and disease susceptibility, prognosis, or the cumulative incidence of AE was assessed.

Results: TERT rs2736100 and MUC5B rs35705950 were significantly associated with IPF risk, and DSP rs2076295 was linked to prognosis and the incidence of AE in IPF patients. TERT rs2736100 was significantly associated with prognosis in IPF patients and the incidence of AE in patients with unclassifiable IIPs. No individuals with the TT genotype of MUC5B rs35705950 were identified, and the proportion of those with the T allele was low (minor allele frequency of 0.005 in control subjects). In addition, no individuals with the minor allele (A) of AKAP13 rs62025270 were detected.

Conclusion: Consideration of genetic polymorphisms has the potential to facilitate prediction not only of prognosis but also of AE in individuals with IIPs, providing a foundation for the development of personalised management strategies based on genetic profiles.