Cis-acting allelic variation in MUC5B mRNA expression is associated with different promoter haplotypes

Mucins play a critical role in protecting and clearing the airways of noxious materials. Genetic variation that influences this environmental response is likely to affect respiratory disease susceptibility. It has been reported previously that variation in the promoter of MUC5B, the gene that encodes one of the two major gel-forming mucins (MUC5B) of the mucus of the respiratory tract, is associated with susceptibility to diffuse panbronchiolitis, and that a genetic difference in promoter activity can be detected in vitro. The aim of this study was to determine whether this genetic difference in promoter activity can be detected in vivo. Here, we undertake RNA transcript expression studies, making use of human fetal tissue to explore constitutive differences. We compare in vivo transcript expression levels in heterozygotes and use the Bayesian method, PHASE to associate exonic simple nucleotide polymorphisms (SNPs) with promoter SNPs to generate haplotypes. We successfully show haplotypic differences in MUC5B expression in vivo. This genetic variation should be taken into account in future studies on MUC5B in respiratory disease.