African American man having pains holding his chest.
Credit: digitalskillet/ Getty Images

The V142I transthyretin variant, present in three to four percent of self-identified Black individuals in the U.S., increases the risk for both heart failure and death and contributes to significant decreases in longevity, according to work by researchers at Brigham and Women’s Hospital and Duke University. 

Their study looked at data from over 20,000 self-identified Black individuals. The researchers estimate that approximately a million years of life will be lost due to this variant among currently living Black individuals who are in mid-to-late life.  

The report was published in JAMA Network yesterday, the lead author is Senthil Selvaraj, MD, Duke University School of Medicine.

This research shows that individuals who carry the V142I transthyretin variant are at significantly increased risk for heart failure beginning in their 60s, and at increased risk for death beginning in their 70s. Further, in this study, carriers on average died two to two and a half years earlier than expected. There are nearly half a million Black Americans carriers over the age of 50.

“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, Brigham and Women’s Hospital and Harvard Medical School.  

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. 

“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,” says Solomon.

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. Since approximately 48 million Americans self-identify as Black, 1.5 million across the lifespan are estimated to carry this variant. However, effects of the variant aren’t typically seen until after age 50.

These 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.

“Since 34 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 Selvaraj. “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.”

Also of Interest