MUC2MUC5B and TOLLIP variants: no association with disease progression and survival in an IPF cohort

The MUC5B variant rs35705950 is a key genetic risk factor for IPF, and has been associated with a more benign disease course. MUC2 rs7934606, and gene variants in TOLLIP, both located at the same locus as MUC5B, have also been associated with IPF in genome wide association studies. TOLLIP rs5743890 has been associated with mortality and TOLLIP rs3750920 with differential responses to treatment in IPF. Our aim was to evaluate the association between these variants and IPF disease progression and survival. DNA was collected from 299 Caucasian IPF patients with a minimum of 6 months follow-up lung function. Baseline composite physiologic index (CPI = 91.0-(0.65 x DLCO % predicted)–(0.53 x FVC % predicted)+(0.34 x FEV1 % predicted)) was used as a marker of disease severity. Mixed effect model analysis for decline in lung function was performed. Time to all-cause mortality was also evaluated using proportional hazards analysis. None of the tested SNPs were significantly associated with decline in any of the measures of lung function: FVC, DLCO, FEV1 and KCO. Univariate and multivariate analysis, including age, gender, smoking history, treatment with pirfenidone/nintedanib, and CPI, showed that none of the tested SNPs were associated with survival. In our cohort, genetic variants in MUC2, MUC5B and TOLLIP were not associated with survival or lung function decline in IPF although our study may not have had the power to detect weak associations, our results suggest that these variants are not strongly related to IPF prognosis. Further study is needed to clarify the key genetic risk factors of disease progression/mortality in the MUC2/MUC5B/TOLLIP genetic region in IPF.