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Study proves genetic variations influence cystic fibrosis' severity

CHAPEL HILL -- Subtle differences in other genes -- besides the defective gene known to cause the illness cystic fibrosis -- can significantly modify the inherited disease's severity, a large new multi-center national study has concluded.

The study, led by University of North Carolina at Chapel Hill and Case Western Reserve University researchers, for the first time shows that particular versions of the transforming growth factor beta 1 (TGFb1) gene are largely responsible for how badly the illness affects patients' lungs.

A report on the findings appears in the Oct. 6 issue of the New England Journal of Medicine.

"As this gene is one of about 30,000 genes in our bodies, its identification as a modifier of the CF lung disease allows us a specific target to focus on for improving CF therapy," said Dr. Mitchell L. Drumm, associate professor of pediatrics and genetics at Case. "As we better understand its function in lung disease, we hope it will allow us to design better and more specific therapies. Because other researchers have found a similar effect of this gene in asthma, the implications likely extend to other disorders affecting the lungs as well."

More than 50 hospitals and medical centers and scores of physicians across the United States and Canada participated in the investigation, which was actually two closely related studies with separate groups of patients. Findings were essentially the same for both, according to principal investigator Dr. Michael R. Knowles, professor of medicine at the UNC School of Medicine.

"This study is especially important in the field of genetic modifiers, because we had enough patients -- over 1,300 -- and a robust study design to assure that our observation is likely correct," Knowles said. "That is in contrast to much of the previous work in this area where the number of subjects was usually too small to be conclusive.

"The observation has tremendous implications about the futur
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Contact: David Williamson
rdtokids@email.unc.edu
919-962-8596
University of North Carolina at Chapel Hill
5-Oct-2005


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