Potential clinical utility of MUC5B und TOLLIP single nucleotide polymorphisms (SNPs) in the management of patients with IPF

Abstract

Background: Genetic variants of TOLLIP and MUC5B, both on chromosome 11, have been reported to be associated with the development and/or prognosis of idiopathic pulmonary fibrosis (IPF). This retrospective study was conducted to investigate the association of MUC5B and TOLLIP SNPs with disease outcome in IPF. 62 IPF patients and 50 healthy controls (HC) from our Institution were genotyped for SNPs within MUC5B (rs35705950) and TOLLIP (rs3750920 and rs5743890). Correlation of SNPs genotypes with survival, acute exacerbation (AE) or disease progression (defined as a decline of ≥ 5% in FVC and or >10% in DLco in one year) was investigated.Results: The MUC5B rs35705950 minor allele (T) was more frequent in IPF subjects than in HC (35% vs 9% p<0.001). TOLLIP SNPs alleles and genotype distribution did not differ between IPF and HC and did not vary according to gender, age, BMI and lung functional impairment at baseline. The minor allele (C) in TOLLIP rs5743890 was associated with worse survival and with disease progression in all performed analyses. The MUC5B rs35705950 or the TOLLIP rs3750920 minor allele, were not associated with disease progression or acute exacerbation. Conclusion: We confirm that the minor allele of MUC5B rs35705950 is associated with IPF. The minor allele of TOLLIP rs5743890 appears to be a predictor of worse survival and more rapid disease progression, therefore being of potential utility to stratify IPF patients at baseline.

DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study

“…In addition, our data from a single registry should be verified with an independent group of IPF patients of different ethnicities. Despite these limitations, our exploratory study on a similarly sized group of patients as another IPF pharmacogenomic studies 5,32,33 demonstrated an association between the profibrotic variant and antifibrotic treatment outcomes.…”

“…32 Other recent study investigated 62 IPF patients on antifibrotic treatment for MUC5B rs35705950 and TOLLIP rs5743890 polymorphisms. 33 This study reported that minor allele C in TOLLIP, an inhibitor of the toll-like receptors (TLRs) 2 and 4, but not MUC5B, was associated with worse survival, acute exacerbation and disease progression. 33 Similarly, in our cohort no association of MUC5B rs35705950 with acute exacerbation IPF nor radiological findings were observed.…”

“…33 This study reported that minor allele C in TOLLIP, an inhibitor of the toll-like receptors (TLRs) 2 and 4, but not MUC5B, was associated with worse survival, acute exacerbation and disease progression. 33 Similarly, in our cohort no association of MUC5B rs35705950 with acute exacerbation IPF nor radiological findings were observed. Other study has shown that the MUC5B variant does not affect oral N-acetylcysteine treatment in IPF.…”

Toll interacting protein (TOLLIP) increases in fibrotic lung tissue of connective tissue disease-associated interstitial lung disease and is associated with clinical outcome

“…In addition to GWAS, some clinical retrospective studies have also demonstrated the function of TOLLIP in IPF. A retrospective study demonstrated that the minor allele (C) in TOLLIP rs5743890 was associated with worse survival and disease progression in patients with IPF [33]. In a post-hoc exploratory analysis of patients enrolled in the clinical trial "Evaluating the Effectiveness of Prednisone, Azathioprine, and N-Acetylcysteine in Patients with Idiopathic Pulmonary Fibrosis", a signi cant correlation was observed between the response to N-acetylcysteine (NAC) therapy and rs3750920 of TOLLIP [34].…”