PAR-4

FRIDAY, July 28, 2023 -- Black people tend to be more vulnerable to suffering severe strokes, but scientists have long struggled to figure out why. Until now: New research suggests it may boil down to having a particular version of a gene involved in clotting. “This could potentially change the entire rubric for how we treat strokes. So it really does have some potential, very, very consequential effect on the treatment of stroke in African Americans,” said Dr. Calvin Smith , an assistant professor of internal medicine at Meharry Medical College in Nashville, Tenn. He was not involved in the research. The study, published July 28 in the Journal of Clinical Investigation , involved mice that had a particular variant of a gene called PAR4 that is found more commonly in Black individuals than white individuals. This variant, the A allele, is found in around 60% of Black people and 20% of white people. PAR4 is associated with greater platelet aggregation, meaning blood clots more easily. The body uses clotting to stop bleeding after injury, but it can also cause a stroke if clots block the flow of blood in the brain. “When platelets become hyper-reactive or become dysfunctional, you can end up having heart attacks and strokes and venous thrombosis,” explained senior study author Robert Campbell , a professor at the University of Utah School of Medicine. “There's good literature to suggest that Black individuals have a higher incidence of stroke. And we decided to look at whether or not mice that have [the variant] ended up having, you know, worse stroke outcomes and worse stroke -- and indeed they do.” At the start of the study, the scientists tested 7,620 Black participants for PAR4 and found that those carrying two copies of the A allele had both higher incidence of stroke and greater disability after a stroke. Next, the researchers turned to mice, replacing one of the mice’s genes with the equivalent of the PAR4 A allele. They found the mice with this version of the gene indeed had worse stroke outcomes, compared to their counterparts without that version of the gene. To dig further still, the authors tested common stroke medications on the mice, such as aspirin and ticagrelor (Brilinta). They found that the drugs protected mice with the PAR4 variant commonly found in white people, but did not protect mice with the PAR4 variant common in Black individuals. Campbell said he hopes his research will highlight the need for more racial diversity in medical trials. “The number of African Americans proportionally versus whites proportionally who submit to studies, who participate in studies, is much lower,” said Smith. “And there are reasons for that. A lot of them are related to mistrust and distrust of the system. And we can go through all of the different reasons, the Tuskegee experiment, the various experiments that were performed on African American women during pregnancy, et cetera, which lead to African Americans not really being very open to being studied and researched." But Smith noted that precision medicine , an emerging field that the U.S. Food and Drug Administration defines as “an innovative approach to tailoring disease prevention and treatment that takes into account differences in people's genes, environments and lifestyles,” depends upon diverse participation in trials. “There's never been a better time for us as African Americans to take part in studies like this, to have our voices heard,” he urged. “If we find that there are significant differences in the treatment based on the medication, we could be putting ourselves at harm by not submitting to these research studies and not allowing for our proper proportion of society to be measured in these types of studies.” Sources Robert Campbell, PhD, internal medicine, assistant professor, pathology, and adjunct assistant professor, University of Utah School of Medicine, Salt Lake City Calvin Smith, MD, primary care doctor, Meharry Medical Group, and assistant professor, internal medicine, Meharry Medical College, Nashville, Tenn. Journal of Clinical Investigation , July 28, 2023 Posted July 2023