Genetic Marker Identified that may Predict Outcomes of Treatments in Patients with Peripheral Artery Disease
News Jul 06, 2011
Results were presented by Michael S. Conte, M.D., of the University of California, San Francisco in a late-breaking clinical trial session at the 2011 Society for Vascular Surgery Annual Meeting in Chicago.
Bypass surgery, angioplasty and stents are all used to treat blockages caused by peripheral artery disease (PAD). Current estimates are that more than 8 million Americans have PAD, a condition that can produce severe disability and lead to amputation. Hundreds of thousands of procedures are performed each year in the US to improve leg circulation in patients suffering from PAD, yet up to half of these fail within a few years due to excessive scarring that leads to reduced blood flow. The reasons for the variability in the outcome of PAD treatments have been poorly understood.
Led by vascular surgeons Dr. Conte and Alec Clowes, M.D. at the University of Washington, the team demonstrated a potential genetic basis for why some patients experience blockage of their bypass grafts faster and more frequently than others.
“The results of this study, together with similar findings in a Dutch study of patients who underwent coronary stent angioplasty (van Tiel et al, 2009), strongly support the hypothesis that the formation of scar tissue in blood vessels is genetically regulated by the gene p27,” stated Dr. Conte.
Dr. Conte is Chief of UCSF’s Division of Vascular and Endovascular Surgery and Chief Medical Officer of Vascular Cures. Dr. Clowes is Professor of Surgery at the University of Washington and Vice Chair for Research in the Department of Surgery.
“These studies represent a major breakthrough in our understanding of arteries closing after angioplasty and bypass grafting,” added Dr. Clowes. “More importantly, they may help us identify patients at increased risk of treatment failures. These results may also accelerate drug development to prevent renarrowing of vascular reconstructions.”
Members of the Vascular Cures Research Network, Dr. Conte and Dr. Clowes performed a gene association study in a group of 204 patients who had undergone leg vein bypass grafting, testing them for a common variation of the gene p27, which is known to control how cells grow. Patients with the -838AA genotype (17% of the patients) were 2.5 times more likely to have a successful graft over patients with either of the more common -838AC or -838CC genotypes. This result remained significant even when controlling for age, gender, diabetes and other clinical factors known to influence surgical outcomes. The study was funded partially by the National Heart, Lung and Blood Institute and Vascular Cures.