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Aspirin Genomics Research Study Goes Global

A Duke study aimed to identify which individuals are most likely to suffer dangerous blood clots despite regular aspirin therapy is about to head overseas. The parallel study soon to begin on patients of Chinese descent is a joint venture of the Duke Institute for Genome Sciences & Policy (IGSP) and the Duke-NUS Graduate Medical School in Singapore.

"This is a real opportunity to set a paradigm for doing pre-clinical genomics research globally," says Geoff Ginsburg, Director of Genomic Medicine at the IGSP.

Blood clots form when irregular cell fragments known as platelets become activated and clump together. For reasons that aren't fully understood, aspirin blocks platelet function to prevent those clots. But aspirin therapy doesn't work for everyone.

"One fifth of patients prescribed aspirin will still go on to have a heart attack or stroke," said Deepak Voora, a Duke cardiologist and member of the IGSP. "Aspirin has been used for decades, but there is little understanding of the genes and pathways involved and of the biological differences that lead some to respond well while others do not. We want to understand those differences."

For the last several years, Ginsburg, Voora and their Duke colleagues have been recruiting healthy volunteers and those with diabetes or coronary artery disease to a study designed to work those biological details out. The work is being done within the Duke Clinical Research Unit, a state-of-the-art facility that brings the latest in 'omics' technologies together with physiological assessments and imaging capabilities. They measure how well participants' platelets work to start and how that changes with a daily dose of aspirin. Then they look for gene patterns that would effectively match those responses.

Previous research on similarities between gene patterns in blood and patients' platelet response to aspirin appears promising, Ginsburg says. The research is also yielding novel biological discoveries. For example, many of the genes they've identified aren't in the pathway that had mainly been thought to explain aspirin's effect on platelets.

Since aspirin is one of the most common and important drugs used worldwide, a question is whether the findings made at Duke in a study population of primarily European ancestry will also apply to those of other ethnicities. That's what the research team hopes to find out through the new Singapore collaboration, conducted in the newly launched SingHealth Investigational Medicine Unit. Voora says they expect to begin enrolling in the Singapore study in early 2012, with hopes to ultimately expand to other research settings around the globe.

"While there are assays available that can measure the effects of aspirin on platelets, these are labor intensive tests that can't be performed in a standard clinical laboratory," Ginsburg said. "Our goal is to develop a robust assay that, once validated, can easily be deployed around the world."