UTHealth scientists discover powerful predictors of congestive heart failure

A team of scientists at The University of Texas Health Science Center at Houston (UTHealth) and Baylor College of Medicine, led by Eric Boerwinkle, Ph.D., Richard Gibbs, Ph.D., and Bing Yu, Ph.D., have identified powerful predictors of congestive heart failure, a major cause of hospitalization and death in the United States. The discovery, published today in Science Advances, was made through an analysis of how gene mutations affect circulating metabolites in the human body.

The human metabolome is a collection of small molecules called metabolites that result from cellular and biological processes in the body and can act as predictors of future disease. Researchers studied how naturally occurring gene mutations can affect metabolites in the genomes of 1,361 African-American participants in the Atherosclerosis Risk in Communities (ARIC) study. ARIC is a longitudinal, population study designed to investigate the origins and predictors of heart disease, stroke and other chronic diseases.

A mutated gene, SLCO1B1, was found to be associated with high levels of blood fatty acid, which is a strong predictor for the development of future heart failure and the mutation itself has a direct effect on heart failure risk.

Because of the aging population, the estimated prevalence and cost of care for heart failure is expected to increase dramatically. By 2030, it's estimated that more than 8 million people in the United States will have heart failure with $70 billion total costs, according to the American Heart Association. A major risk factor of heart failure is high blood pressure, or hypertension, which is more common among African-Americans.

"The key to heart failure is to identify those at increased risk early. Our hope with this discovery is that we can be more aggressive in treating hypertension if we know someone is genetically predisposed to heart failure," said Boerwinkle, Kozmetsky Family Chair in Human Genetics and dean of UTHealth School of Public Health.

While the finding was made in a population of African-American participants, the researchers were able to confirm the relationship among European Americans as well.

"African-Americans have higher rates of hypertension, heart failure and mortality. We would expect our findings can help in the prediction and prevention of heart failure among African Americans," said Yu, assistant professor in the Department of Epidemiology, Human Genetics and Environmental Sciences at UTHealth School of Public Health.

The research builds upon the group's work on "knockout humans," which are naturally occurring mutations that inactivate a certain gene. A typical human exome has dozens of these loss-of-function gene variants. Last year, using this technique, the team identified eight new relationships between genes and diseases.

This paper is the first to examine how mutated genes directly affect the metabolome on a genome-wide scale and then go on to influence disease risk. By studying these relationships, the researchers have discovered a new pathway to identify how genes influence disease, according to Boerwinkle.

Source:

University of Texas Health Science Center at Houston

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