Scientists Identify Gene that Controls Clotting

Oct. 27, 2014

Researchers at the Aab Cardiovascular Research Institute (CVRI) have identified a gene that controls how our blood clots, an important biological process that requires a fine balance: Too little clotting leads to excessive bleeding and too much leads to blockages in our blood vessels.  Variations within this gene may explain why some people form clots more easily than others and are at greater risk of deep vein thrombosis (a blood clot that forms in a vein deep in the body and can break off and block blood flow to other parts of the body), heart attack and stroke.Beating heart

The study, published in the Journal of Clinical Investigation, started with scientists at the National Institutes of Health’s Framingham Heart Study who analyzed the genes of more than 20,000 humans and discovered eight that were closely linked to clotting function. Senior study author Charles J. Lowenstein, M.D., director of CVRI, explored the role of one of those genes, STXBP5, in mice and human cells. He found that STXBP5 regulates how cells release messenger molecules that spur the formation of blood clots.

Lowenstein, who is also the chief of Cardiology at UR Medicine’s Strong Memorial Hospital, says that 40 percent of people have mutations in the STXBP5 gene, which could lead to abnormal clotting. His team plans to study how these mutations affect bleeding and clotting in mice and human cells. He believes that this work is a step towards the genetic testing of patients who are at risk for deep vein thrombosis, including people who are over the age of 60, overweight or obese, being treated for cancer and smokers. Knowledge of a person’s specific mutation could allow for the administration of tailored treatments that offer the greatest benefit to the patient.

The research was funded by a National Heart Lung and Blood Institute grant to Lowenstein, a Howard Hughes Medical Institute grant to Lowenstein and lead study author Qiuyu Zhu, a graduate student in the Lowenstein lab, and American Heart Association grants to Lowenstein, Zhu and Munekazu Yamakuchi.  Read more about the study here.