Researchers show that the genetic variant common in black Americans contributes to the high burden of cardiovascular disease

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Researchers from Brigham and Women’s Hospital and Duke University have shown that a genetic variant, present in 3-4% of self-identified black individuals in the US, increases the risk of heart failure and death and contributes to a significant decrease in lifespan of the population. level

A genetic variant carried by 3-4 percent of self-identified black Americans increases the risk of heart failure and death, contributing to a significant decline in lifespan at the population level, according to a new study led by researchers at Brigham and Women’s Hospital. a founding member of the Mass General Brigham health care system and the Duke University School of Medicine. The new research shows that individuals who carry the V142I transthyretin variant have a significantly increased risk of heart failure from the age of 60, with an increased risk of death from the age of 70. Furthermore, the researchers showed that carriers died on average 2 to 2.5 years earlier than expected. With nearly half a million Black Americans over the age of 50, researchers estimate that approximately one million years of life will be lost among currently living Black individuals in mid- to late-life due to this variant. Results have been published in JAMA.

“We believe these data will inform physicians and patients about the risks when these genetic findings are known, whether through family screening, medical or even commercial genetic testing,” said senior author Scott D. Solomon, MD, the Edward D. Frohlich Distinguished Chair. , professor of medicine at Brigham and Women’s Hospital and Harvard Medical School. “There are now several potential new therapies for cardiac amyloidosis, and understanding the magnitude of this risk, at the individual and societal level, will help determine which patients are best suited for new therapies.”

The V142I variant causes transthyretin, a protein in the blood, to misfold, leading to deposits of abnormal amyloid protein in the heart and other parts of the body. In the heart, these deposits cause muscles to become thick and stiff, a condition known as cardiac amyloidosis that can eventually lead to heart failure. Recently, several therapies have been developed to treat cardiac amyloidosis, including ones that: prevent the protein from misfolding, reduce the amount of protein, remove the protein, and even a gene editing therapy that is currently undergoing clinical trials. Better understanding the epidemiology of V142I and cardiac amyloidosis would help doctors connect patients to the right treatment at the right age, the researchers say.

Although the association between the V142I variant and heart failure has been previously described, precise estimates of how the variant increases risk have been unclear until now. Since approximately 48 million Americans identify as black, an estimated 1.5 million Americans will carry this variant over their lifetime. However, because the variant’s effects are typically not seen until after age 50, researchers focused on the risk among Black Americans in mid- to late life.

To uncover these details, the researchers pooled data from self-reported black participants in four NIH-funded studies in the United States (ARIC, MESA, REGARDS, and Women’s Health Initiative). In total, the team examined data from 23,338 self-reported black individuals, of whom 754 (3.23 percent) carried the V142I genetic variant.

They showed that V142I increased the risk of hospitalization for heart failure at age 63 and the risk of death at age 72. The contribution of the variant to the risk of heart failure increased significantly with age, but was not itself increased by other known risk factors such as diabetes and hypertension. The team also showed that female and male carriers of the variant were at equal risk, unlike previous studies that showed men were more affected. This suggests that women are likely underdiagnosed with the condition. The researchers estimate that individual carriers with the V142I variant will live 2 to 2.5 years shorter than expected.

“Since 3 to 4 percent of self-identified black individuals in the United States carry this variant, a significant number are at increased risk of developing cardiac amyloidosis, being hospitalized for heart failure, and dying several years earlier than expected,” said the first author. Senthil Selvaraj, MD, an advanced physician-scientist in heart failure at Duke University School of Medicine. “With our improved understanding of the variant’s risks, future efforts to increase disease awareness and ultimately connect carriers with the disease to effective therapies will be important.”

In future studies, the researchers want to investigate why some, but not all, carriers of the V142I variant develop cardiac amyloidosis. They are also actively involved in developing and testing therapies for the disease, including the gene therapy mentioned above.

“One of the areas that will be very important in the future is whether we can actually prevent the onset of the disease if we identify these patients earlier,” Solomon said.

Other Brigham authors include Brian Claggett and JoAnn E. Manson. Other authors include Robert J. Mentz, Svati H. Shah, Michel G. Khouri, Ani W. Manichaikul, Sadiya S. Khan, Stephen S. Rich, Thomas H. Mosley, Emily B. Levitan, Pankaj Arora, Parag Goyal , Bernhard Haring, Charles B. Eaton, Richard K. Cheng, Gretchen L. Wells and Marianna Fontana.

More information:
Selvaraj, S et al. Cardiovascular burden of the V1421 transthyretin variant, JAMA (2024). DOI: 10.1001/jama.2024.4467

Provided by Brigham and Women’s Hospital


Quote: Researchers show genetic variant common in Black Americans contributes to major burden of cardiovascular disease (2024, May 12), retrieved May 12, 2024 from https://medicalxpress.com/news/2024 -05-genetic-variant-common-black-americans. html

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