Genotype in MUC5B-Promoter Polymorphism and Chronic Lung Allograft Dysfunction (CLAD) in a German Cohort: Preliminary Results

Abstract

The long-term survival of lung transplant recipients is significantly limited by the occurrence of chronic lung allograft dysfunction (CLAD). A single nucleotide polymorphism (SNP) in the promoter region of the MUC5B-gene (rs35705950) has been identified as an independent risk factor for the development of idiopathic pulmonary fibrosis (IPF). Moreover, MUC5B genotype is associated with survival in IPF patients. Aim of the study was to investigate whether the development of CLAD is associated with genotype in MUC5B-promoter polymorphism. 73 patients, who underwent lung transplantation from 1998 to 2015 for several indications, and 50 healthy controls were retrospectively studied. CLAD was defined as persistent decline of FEV1 to < 80 % of the post-transplant baseline. MUC5B rs35705950 SNP genotype was detected by real time PCR and pyrosequencing. During the follow-up period of 8 ± 4 years, 51 % of patients developed CLAD. MUC5B rs35705950 alleles were in Hardy-Weinberg equilibrium and genotype distribution did not differ between healthy controls and transplant recipients. 53 % of the patients carrying the GG genotype and 40 % of the patients carrying the GT genotype group developed CLAD (p=0.398). No correlation between MUC5B rs35705950 genotype and age, gender, lung function tests and survival was found. In our cohort, genotype in the MUC5B-promoter polymorphism was not associated with the development of CLAD or survival.