Black American populations have a higher risk of stroke and tend to experience more severe stroke outcomes than White populations.

Now, researchers at University of Utah Health have found that differences in a gene involved in blood clotting may contribute to this disparity, affecting both the severity of the stroke and which stroke medications are effective.

The gene, called PAR4, helps blood cells called platelets clump together into clots – a necessary part of the body’s injury response, but one that can turn deadly if clots block blood flow to the brain, causing a stroke. Different people can have different versions of the PAR4 gene, and one version, the A variant, is more common in Black Americans than in White populations.

The research team asked whether variability in PAR4 could explain some of the difference in stroke severity between these populations.

The researchers compared stroke outcomes within a group of 7620 Black patients, some of whom had the A variant. They found that patients with two copies of the A variant had a higher risk of stroke and more severe post-stroke outcomes than other patients.

But the scientists didn’t know if the A variant was actually causing the increased risk, since other factors – like environment, lifestyle, or differences in other genes – could be affecting the trend they saw. To figure out whether the A variant itself increases stroke severity, they tested if differences in the gene changed stroke outcomes in mice, where they could keep all other variables the same – an impossible and unethical task in human trials. As the researchers predicted, mice with the A variant had more severe strokes.

The researchers found that variation in the gene can impact not only the initial severity of a stroke, but also the effectiveness of common stroke-preventative medications like aspirin and ticagrelor. These medications improve stroke outcomes in mice without the A variant, but didn’t help mice with the A variant. But a less commonly used stroke medication did improve stroke outcomes for both groups.

The results underscore the importance of including diverse populations in clinical trials to get a more complete picture of a treatment’s effectiveness.

Ultimately, this work could help reduce racial disparities in stroke outcomes by improving stroke prevention and treatment.