A team of researchers from the University of Michigan (U-M) in Ann Arbor and other universities recently published a study in which they described their discovery of part of the human genome responsible for regulating von Willebrand factor (VWF) levels. VWF is an important clotting factor protein that plays a significant role in blood coagulation. While lower levels of VWF are linked to prolonged bleeding in patients with disorders such as von Willebrand disease (VWD), higher levels may contribute to excessive blood clots, stroke and heart attacks.
The lead author of the report was David Ginsburg, MD, a faculty member in the Life Sciences Institute; a professor of internal medicine, human genetics and pediatrics at the U-M Medical School; and a Howard Hughes Medical Institute investigator. Ginsburg heads a lab that focuses on genetic studies of blood coagulation and thrombosis, including a longtime interest in VWF and the genetics of VWD.
Although earlier studies have identified two genes partially responsible for VWF levels, this only partly explains how inherited disparities generate varying levels of the key protein in individuals. While age and environment can also affect VWF levels, a comprehensive explanation is still lacking. Ginsburg and his team began soliciting blood donations from siblings with normal VWF activity in 2006, eventually focusing on two cohorts of younger siblings all in their early 20s. Younger siblings were chosen because they were less likely to be affected by environmental factors, such as aging and smoking.
The investigators first conducted a genome-wide association study in which they were able to corroborate the presence of the two previously identified genes related to VWF levels. They then scanned specific sections of the genome consistent in both siblings, identifying a VWF-regulating gene on a segment of chromosome 2. This discovery has not been found in previous studies with subjects who were unrelated.
Next, Ginsburg and colleagues plan to locate the exact gene on chromosome 2. Once the gene is identified, they will look for ways in which the gene might differ among individuals. These differences may be linked to VWF levels and correspond with increased risk for prolonged bleeding or excessive clotting. Findings from these studies may eventually provide greater insight to enhance the diagnosis of bleeding and clotting disorders, and to trigger breakthroughs in treatment and clinical management.
The report, “Linkage Analysis Identifies a Locus for Plasma von Willebrand Factor Undetected by Genome-Wide Association,” was published in the January 8, 2013 issue of the Proceedings of the National Academy of Sciences.
Source: ScienceDaily, January 8, 2013