MUC5B (rs35705950) Polymorphism and Its Association With Serum Krebs Von Den Lungen-6 (KL-6) and Matrix Metalloproteinase-7 (MMP7) in Patients With Interstitial Lung Disease (ILD) From India

Purpose Krebs von den Lungen-6 (KL-6) and matrix metalloproteinase-7 (MMP7) are established serum biomarkers for interstitial lung disease (ILD). A combination of KL-6 and MMP7 may be a useful screening tool for patients at risk of ILD. However, data on their association with MUC5B promoter polymorphism (rs35705950) in Indian ILD patients are lacking. There is a gap in knowledge of MUC5B genotypes in different subtypes of ILD and the diagnostic cut-offs of serum KL-6 and MMP7 in ILD patients from India. The primary aims of this study were to evaluate the proportion of MUC5B promoter polymorphism in different subtypes of ILD and to establish diagnostic cut-offs for serum KL-6 and MMP7 to distinguish ILD patients from healthy controls. The secondary aim was to investigate whether there was any genotype-phenotype association between the MUC5B genotype and serum biomarker levels. Methods This cross-sectional study was conducted in 200 ILD patients from a tertiary care institute in India. Serum KL-6 and MMP7 levels were measured using ELISA. Genotyping for MUC5B (rs35705950) was performed using DNA extracted from peripheral blood leukocytes. Results Connective tissue disease-associated interstitial lung disease (CTD-ILD) was the most common ILD subtype (45%). KL-6 levels were higher in idiopathic pulmonary fibrosis (IPF) than fibrotic hypersensitivity pneumonitis (fHP) (105.6 ng/mL vs. 65.87 ng/mL; p=0.0409), in patients who died (109.8 ng/mL vs. 68.6 ng/mL; p=0.022), and in the MUC5B (rs35705950) GT/TT genotype (85.07 ng/mL vs. 65.58 ng/mL; p=0.019). MMP7 levels were higher in IPF than CTD-ILD and fHP (14.01 ng/mL vs. 8.690 ng/mL and 7.970 ng/mL; p=0.0175 and p=0.0118, respectively). The minor MUC5B T allele was more frequent in all ILD subtypes. Conclusion This study established an association between MUC5B (rs35705950) promoter polymorphism and higher serum KL-6 levels. The T minor allele had a higher frequency in all ILD subtypes. The study also established cut-offs of serum KL-6 and MMP7 to distinguish between Indian ILD patients and controls.