Potential Clinical Utility of MUC5B and TOLLIP Single Nucleotide Polymorphisms (SNP) in the Management of Patients with IPF: Preliminary Results

Background Genetic variants of TOLLIP and MUC5B (both on Chr 11) have been reported to be associated with development and/or the prognosis of idiopathic pulmonary fibrosis (IPF). Real-life experiences on the application of SNPs in the clinical management of IPF are lacking. This study was conducted to investigate the association of MUC5B and TOLLIP SNPs with disease course and outcome in a single-centre cohort.
Patients and Methods 50 IPF patients (M 43 and F 8, age 66 ± 10 y) and 50 healthy controls (HC) (M 37, F 13, age 42 ± 2 y) were genotyped for SNPs within TOLLIP (rs3750920 and rs5743890) and MUC5B (rs35705950). Diagnosis of IPF was made according to the ATS/ERS guideline 2011. Genotype frequency was compared between IPF and HC subjects. Correlation of SNPs genotypes with survival, acute exacerbation or disease progression (a decline of ≥ 10% in FVC) was investigated.
Results TOLLIP SNPs allele and genotype distribution did not differ between IPF and HC (p = 0.6) whereas the MUC 5B T minor allele was more frequent in IPF subjects than in HC (p = 0.0001). The SNPs genotypes did not correlate with the incidence of acute exacerbation or with survival. A higher proportion of patients with the TOLLIP rs5743890 SNP minor allele had disease progression in comparison to patients with the major allele (chi square = 26.8, p < 0.0001). For TOLLIP rs3750920 or MUC5B rs35705950 no association with disease progression was found.
Conclusion We confirm that the minor allele T in MUC5B SNP is associated with IPF. TOLLIP gene variants appear to correlate with disease progression, therefore being of potential utility to stratify IPF patients.