A recent study conducted by researchers at Brigham and Women’s Hospital and Duke University reveals that a genetic variation found in 3-4% of self-identified Black individuals in the U.S. significantly increases the risk of heart failure and death, leading to a notable decrease in lifespan at the population level (1^✔ ✔Trusted Source
Cardiovascular Burden of the V142I Transthyretin Variant

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).

The study, published in JAMA, demonstrates that individuals carrying the V142I transthyretin variant face a heightened risk of heart failure in their 60s and an increased risk of mortality in their 70s. On average, carriers die 2 to 2.5 years earlier than expected, resulting in an estimated loss of approximately one million years of life among current Black individuals aged 50 and above.

The Impact of the V142I Variant on Cardiac Amyloidosis

“We believe these data will inform clinicians and patients regarding risk when these genetic findings are known, either 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 might be best suited for novel therapies (2^✔ ✔Trusted Source
Rare gene mutation in some Black Americans may allow earlier screening of heart failure

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).”

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 the muscle to become thick and stiffened, a condition known as cardiac amyloidosis, which can ultimately lead to heart failure. Recently, several therapies have been developed to treat cardiac amyloidosis, including therapies 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. A better understanding of the epidemiology of V142I and cardiac amyloidosis would help physicians connect patients with the appropriate treatment at the appropriate age, the researchers say.

Impact of the V142I Variant on Heart Failure Risk Among Black Americans

Although the association between the V142I variant and heart failure has been previously described, precise estimates of how the variant increases risk were unclear until now. Considering approximately 48 million Americans self-identify as Black, 1.5 million across the lifespan are estimated to carry this variant. However, since effects of the variant aren’t typically seen until after age 50, the 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). Altogether, the team examined data from 23,338 self-reported Black individuals, 754 (3.23 percent) of whom carried the V142I genetic variant.

They showed that V142I increased the risk for heart failure hospitalization by age 63 and the risk of death by age 72. The variant’s contribution to heart failure risk increased substantially 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 equally at risk, contrary to some previous studies showing that men were more affected. This suggests that women are likely underdiagnosed with the condition. The researchers estimated that individual carriers with the V142I variant live 2-2.5 years less than expected.

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

In future studies, the researchers plan 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 really important going forward will be whether we can actually prevent the onset of the disease if we identify these patients earlier,” said Solomon.

References:

1. Cardiovascular Burden of the V142I Transthyretin Variant
   – (https://jamanetwork.com/journals/jama/fullarticle/2818877)
2. Rare gene mutation in some Black Americans may allow earlier screening of heart failure
   – (https://www.nih.gov/news-events/news-releases/rare-gene-mutation-some-black-americans-may-allow-earlier-screening-heart-failure)

Source-Medindia