They report that a restricted set of candidate genes potentially underlie the heightened proliferative properties of adenotonsillar tissues.
Scientists from the University of Chicago have found that a specific gene product may be responsible for the proliferation of adenotonsillar tissue, which can cause pediatric obstructive sleep apnea (OSA).
“We found that in the tonsil tissues of children with OSA, certain genes and gene networks were overexpressed,” states David Gozal, M.D., professor and chair of the department of pediatrics, who led the study. “We believe that the result of this gene overexpression is increased proliferation of the adenotonsillar tissues, which in turn can cause partial or complete obstruction of the upper airways during sleep.”
The findings have been published online ahead of print in the American Journal of Respiratory and Critical Care Medicine. The paper is titled “Transcriptomic Analysis Identifies Phosphatases as Novel Targets for Adenotonsillar Hypertrophy of Pediatric OSA.”
Dr. Gozal and colleagues recruited 18 children with OSA and 18 age-, gender-, and ethnicity-matched children with recurrent tonsillar infections (RI), all of who underwent surgery to have their tonsils removed. The tonsil tissue from each subject was analyzed for relative expression of the 44,000 known genes in the human genome. The researchers then further analyzed the gene pathways to determine which changes may represent differences with a high likelihood of impact on cellular proliferation.
“We wanted to find the most important and functionally pertinent genes, those with the most connectivity,” Dr. Gozal explains. “We identified 47 genes and among those, two specific genes, both phosphatases, which are known to be very important at regulating communication in cells.
“Then we looked at the expression of the phosphatase protein and found that children with OSA have a higher level of phosphatases in the tonsils.” In particular, they focused on one protein called phosphoserine phosphatase (PSPH) that was expressed in children with OSA but almost never expressed in the children with RI.
Dr. Gozal’s team then went on to assess whether phosphatase was a potential target for therapy. They found that introducing calyculin, a phosphatase inhibitor, reduced cell proliferation and increased programmed cell death in the tonsils of OSA patients. “Together, these observations suggest that PSPH is a logical therapeutic target in reversing adenotonsillar enlargement in pediatric OSA,” Dr. Gozal notes.