Understanding Cystic Fibrosis Transmembrane Conductance Regulator expression in Heart Failure

Abstract

Cardiovascular disease, specifically congestive heart failure, is a leading cause of death in the United States. Cystic Fibrosis (CF) is caused by the mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene. These mutations result in a defective or absent CFTR protein in the lung epithelial cells. Not a well-known concept is that the CFTR protein is present in more than just the lungs - its presence in the cardiac tissue may be critical for heart function. Preliminary research from the Bowles lab demonstrates that CFTR expression and function are reduced in diseased human cardiac tissue. Also, DNA sequencing suggests a potential cause for this diminishment: a genetic enhancer in the CFTR gene is different in heart failure patients compared to healthy controls. This difference has been seen in a small study of 48 patients. In this independent study, I examined the CFTR gene through PCR and gel electrophoresis analysis, as well as consolidating previous work from the Bowles lab and others in the CFTR field, to provide an in depth look at this region of the gene. The challenges of this PCR study have held back results of amplification data due to complications with the protocol and electrophoresis. Near the end of the study, successful PCR and gel electrophoresis was completed, showing the technique was achievable after trouble-shooting. This technique will be applied to a larger sample set of genomic DNA to be amplified and sequenced. This study may set the stage for using the CFTR enhancer region as a biomarker of heart failure. In addition, it may provide preliminary data to the Bowles lab for the use of CFTR modulation in the treatment of heart failure.