Arterial and Joint Calcifications May Have Genetic Basis
NT5E mutations found in affected members of three families
THURSDAY, Feb. 3 (HealthDay News) -- Researchers may have identified a genetic basis for symptomatic arterial and joint calcifications, according to research published in the Feb. 3 issue of the New England Journal of Medicine.
Cynthia St. Hilaire, Ph.D., of the National Institutes of Health in Bethesda, Md., and colleagues performed clinical, radiographic, and genetic studies of members of three families with symptomatic arterial calcifications to study the genetic basis of arterial classifications.
The researchers found that nine individuals had arterial calcifications; five were siblings in one family, three were siblings in the second, and one patient was identified from the third family. All three families had NT5E mutations that resulted in nonfunctional CD73. Cultured fibroblasts from affected members of the first family had substantially reduced expression of NT5E messenger RNA, CD73 protein, and enzyme activity, as well as increased alkaline phosphatase levels and accumulated calcium phosphate crystals. The researchers found that genetic rescue experiments normalized the CD73 and alkaline phosphatase activity in affected family members' cells and that adenosine treatment decreased the levels of alkaline phosphatase and calcification.
"We identified mutations in NT5E in members of three families with symptomatic arterial and joint calcifications. This gene encodes CD73, which converts AMP to adenosine, supporting a role for this metabolic pathway in inhibiting ectopic tissue calcification," the authors write.
Several authors are listed as inventors on a patent for the use of adenosine agonists to prevent arterial vascular calcification disorder.