American Thoracic Society, American Journal of Respiratory Cell and Molecular Biology, 5(53), p. 607-614, 2015
Full text: Download
BPIFA1 and BPIFB1 are putative innate immune molecules expressed in the upper airways. Due to their hypothesized roles in airway defense, these molecules may contribute to lung disease severity in cystic fibrosis (CF). We interrogated BPIFA1/BPIFB1 SNPs in data from an association study of CF modifier genes and found an association of the G allele of rs1078761 with increased lung disease severity (p=2.71 x 10-4). We hypothesized that the G allele of rs1078761 is associated with decreased expression of BPIFA1 and/or BPIFB1. Genome-wide lung gene expression and genotyping data from 1,111 individuals with lung disease, including 51 CF patients, were tested for associations between genotype and BPIFA1 and BPIFB1 gene expression levels. Findings were validated by qPCR in a subset of 77 individuals. Western blotting was used to measure BPIFA1 and BPIFB1 protein levels in 93 lung and 101 saliva samples. The G allele of rs1078761 was significantly associated with decreased mRNA levels of BPIFA1 (p=4.08 x 10-15) and BPIFB1 (p=0.0314). These findings were confirmed with qPCR and western blotting. We conclude that the G allele of rs1078761 may be detrimental to lung function in CF due to decreased levels of BPIFA1 and BPIFB1.