Funded Research

Genetic Modifiers of Elastin Insufficiency
Principal Investigator(s):
  • Beth Kozel, M.D., Ph.D. Pediatrics
  • Congenital Heart Disease Center
Award Mechanism:
Faculty Recruitment/Scholar Award
Project Period:
7/1/2011 - 8/21/2015
Total Amount:
Elastin is the primary molecule responsible for recoil in tissues that undergo repeated stretch and release cycles, such as the blood vessels, lungs and skin. People who have genetic changes affecting elastin have narrow, stiff blood vessels, high blood pressure, and lax skin. In the families in which these genetic changes run, the first child may be mildly affected but the next child’s condition may be more severe, requiring lifesaving vascular surgery in their early years. It is unknown what causes this variability. To understand these differences, Dr. Kozel’s lab is using a mouse model of elastin insufficiency to identify other gene changes that raise or lower the risk for blood vessel disease in individuals with decreased elastin. To date, her work has identified several candidate genes predicted to affect blood pressure and blood vessel size. Future studies are planned to determine how medications can be directed in response to these genes to improve vascular health in mice with elastin insufficiency. At the same time, Dr. Kozel is working with a group of patients with Williams- Beuren syndrome, a condition caused, in part, by decreased elastin to determine if the genes that increase the risk of blood vessel disease in mice are also affected in people. Identification of modifiers may allow physicians to provide parents with better information about what to expect in regard to cardiovascular risks for their child with elastin insufficiency and offers the potential to identify new medications that will protect the cardiovascular health of these children.