Newly identified gene may be responsible for sex-linked effects on heart disease outcomes in women

When diagnostic tests for the heart were first created, scientists at the time did not fully consider that no two bodies were the same, especially between genders.

According to Jennifer Dungan, an associate professor at the University of Florida College of Nursing, many of the current symptom profiles and lab tests for heart disease do not accurately reflect known differences in heart disease in women. This omission has led to increased gaps in health care equity.

Because of this disparity, women are more likely than men to report symptoms of heart disease that seem out of the norm, to experience delayed treatment for heart disease, and even to have undiagnosed heart attacks. For reasons that remain unclear, women may experience heart disease differently than men. This can lead to inequalities for women that need to be corrected. »

Jennifer Dungan, Associate Professor, University of Florida College of Nursing

Dungan said cardiology researchers believe some of these differences in symptoms and outcomes may be due to genetic variation between men and women. She identified a specific gene she thinks may be responsible, named RAP1GAP2.

“RAP1GAP2 is a strong candidate for sex-related effects on heart disease outcomes in women,” Dungan said. “Certain DNA markers in this gene are believed to manage the activity of platelets, colorless blood cells that help our blood clot. This also poses a risk of heart attack. An overactive gene could cause too many platelets to respond to the clot , which could block the flow of blood and oxygen to the heart muscle and lead to a heart attack.”

Since RAP1GAP2 was not linked to poor heart outcomes in men in her team’s study, she thinks this gene may work differently in women. His team included professors from UF’s faculties of medicine, pharmacy, and public health and health professions. Their findings were recently published in American Heart Journal Plus.

Even less is known about these racial and ethnic differences. Black women and some Hispanic women are at even higher risk for heart problems, due to many factors that Dungan says can include genetics.

Unfortunately, traditional methods of studying racial and ethnic groups tend to produce results that are irrelevant, Dungan said.

“The goal is not to find biological differences between groups of people. Rather, our goal is to find the genetic markers most accurately linked to heart disease for all women,” she said. “And to do that, we also need to consider genetic variation in females.”

To find out how the gene may impact heart disease risks in women from different backgrounds, Dungan’s latest project, supported by a two-year grant from the National Institute on Aging, a division of the National Institutes of Health, aims to find the specific RAP1GAP2 gene the markers most strongly correlated with disease symptoms, heart attacks and death in women of different racial and ethnic groups.

Using health data from 17,000 postmenopausal women, Dungan and her team will use statistical genetics methods to analyze whether there is a link between certain DNA markers on RAP1GAP2 and heart disease. His team will also use genetic ancestry markers rather than arbitrary racial categories to account for the natural diversity of our genetic code. According to Dungan, this will ensure that his team finds genetic markers that reflect heart disease risk for all women, not just certain groups.

“At the end of the study, if the RAP1GAP2 genetic markers accurately reflect women’s heart symptoms and predict their likelihood of a future heart attack, stroke, or death, these genetic markers could help them be more confident in their diagnosis and future prognosis,” she added. said. “Having more accurate biomarkers for women would save lives and improve health equity for all women.”

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