CHAPEL HILL - Subtle differences in other genes—besides the defective
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
“This study is especially important in the field of
Initially, the study involved 808 CF patients who had inherited an altered form of a gene known as delta F508 from both parents. The second study involved 498 people with the condition. By measuring the volume of air when patients’ exhaled strongly into a machine, researchers determined how severe each subject’s lung disease was.
Scientists then correlated patients’ level of illness against various genetic mutations and found that variants of a gene known as TGFb1 were associated with worse disease. The findings appear to exonerate certain other previously suspected mutations.
Besides Drumm and Knowles, authors of the report include Drs. Fred A. Wright and Fei Zou, associate professor and assistant professor of biostatistics, respectively, at the UNC School of Public Health, and, at Case, Drs. Mark D. Schluchter and Michael Konstan, professors of pediatrics; and Dr. Katrina Goddard, associate professor of epidemiology and biostatistics. Thirteen other scientists and clinicians also contributed to the work and were listed as co-authors.
In an accompanying editorial, Drs. Christina K. Haston and Thomas J. Hudson of McGill University in Montreal praised the new study.
“There are many lessons about modifier genes to be extrapolated from this study, starting with recognition of the tremendous importance of the study design,” Haston and Hudson wrote.
Among its strengths, they said, were its large size—which is essential for such studies if they are to be useful—that it focused on a single class of gene variation and that it took into account numerous possible confounders such as sex, other illnesses like asthmas, enrollment sites, associated diseases and infections.
“There are likely a number of gene modifiers in CF and other diseases, and this current paper describes one of the first robust examples,” Knowles said. “Some CF patients may do worse because of ‘severe
Support for the investigations came from the Cystic Fibrosis Foundation, the National Institutes of Health, Genome Canada and the Canadian Cystic Fibrosis Foundation. Additional support came from the UNC School of Medicine’s genetics department and Dr. William F. Marzluff, executive associate dean for research at the medical school and professor of biochemistry and biophysics. '
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Note: Knowles can be reached at (919) 966-1077 or firstname.lastname@example.org. Drumm can be reached at email@example.com.
News Services contact: David Williamson, (919) 962-8596