Cystic fibrosis (CF) is one of the most common autosomal recessive genetic disorders in the United States, and it results from deleterious mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Because the disease is autosomal recessive, patients with CF must have two defective copies of the gene. CF heterozygotes, individuals carrying only one defective copy of the CFTR gene, have been routinely informed that they are not at increased risk for disease. However, recent studies show that CF heterozygotes may be at risk for many of the diseases traditionally associated with CF, especially respiratory infections.
Philip Polgreen, MD, MPH, professor in Infectious Diseases, and his collaborators received a five-year, $3.7M R01 grant from the National Institute of Allergy and Infectious Diseases. This funding will support the upcoming project titled, “Estimating the risk for and severity of respiratory infections attributable to CFTR heterozygosity.”
Previous studies have used smaller samples, but thanks to the growth in genetic counseling, frequent CFTR mutation testing has identified a large population of CF heterozygotes to study. Specifically, the research team will estimate the risk of respiratory infections associated with being a CF heterozygote and determine if outcomes for respiratory infections are more severe for CF heterozygotes.
The overarching hypothesis of this work is that CF carriers are at greater risk for respiratory infections because they have decreased CFTR function. “Because there are between 10 and 15 million heterozygotes in the US,” Polgreen said, “the burden of respiratory infections attributable to the CF carrier state is likely substantial.” To specifically test this theory, the research team will use a functional assay derived from human respiratory epithelial cultures collected from CF carriers.
The interdisciplinary research team supported by this proposal includes Mahmoud Abou Alaiwa, MD; Joseph Cavanaugh, PhD; Shelby Francis, PhD; Doug Hornick, MD; Aaron Miller, PhD; Alejandro Pezzulo, MD; David Stoltz, MD, PhD; and Joseph Zabner, MD.