New Genome-wide Study Identifies Five Genetic Regions Involved in Cystic Fibrosis Disease Severity

New Genome-wide Study Identifies Five Genetic Regions Involved in Cystic Fibrosis Disease Severity

A new study, conducted by International CF Modifier Consortium and published in Nature Communications, reports the discovery of five regions of the human genome associated with cystic fibrosis (CF) severity.

CF is a life-threatening genetic disorder, characterized by the build-up of mucus in the lungs and obstruction of airways, making patients more vulnerable to infections. The disease is caused by the inheritance of two defective copies of the CFTR gene. Although thousands of mutations of the CFTR gene are known, the severity of the disease shows major variation even between patients with the same CFTR mutation. This is particularly obvious when a new drug targeting a specific mutation, such as the common Delta-F mutation, works partially for some CF patients, but is completely ineffective for others.

The five genome locations recently identified play a role in disease variation by creating proteins that interact with the CFTR gene or protect lung tissue from deterioration, as explained by the senior co-author of the paper Garry Cutting, MD, professor of pediatrics and medicine at Johns Hopkins, “[Some of these genes] play important supporting roles to make sure the CFTR protein and other proteins and protective mechanisms work properly. We need to influence these modifier proteins in order to lessen the severity of disease for patients.”

These findings are the result of a genome-wide study of cystic fibrosis that began in 2000 and included samples from 6,365 CF patients from several cystic fibrosis centers. The results can have an impact on drug discovery and improvement of lung function, as noted by Preston Campbell, MD, executive vice president for medical affairs for the Cystic Fibrosis Foundation, “Identifying the genetic underpinnings for differences in CF lung disease will hopefully inform our precision medicine efforts and spur further drug development.”

The Consortium, formed by researchers from UNC, the University of Toronto, Johns Hopkins University, Case Western University, and the University of Paris, studied more than 8.5 million SNPs (single nucleotide polymorphisms) and found, on chromosomes 3, 5, 6, 11, and X, five genetic variations with significant effects on lung disease.

As a result of this report, researchers from the University of North Carolina School of Medicine / UNC Marsico Lung Institute and Case Western University are already developing and testing drugs targeting two of these variations. Ongoing work related to these exciting findings has as a final goal the discovery of personalized therapy to decrease disease severity and ultimately improve quality of life and longevity for CF patients.

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