Lindsey Shapiro, PhD, science writer —

A genetic variant in TTR — the gene implicated in familial amyloid polyneuropathy (FAP) — was linked with a greater risk of heart failure and death among Black people living in the U.S. in a recent study. In fact, being a carrier of the specific mutation, called Val122Ile, "was significantly associated with an increased risk of heart failure," according to researchers. "Given the relatively higher prevalence of this variant in individuals with African ancestry, the findings support the greater inclusion of historically marginalized racial and ethnic groups in cardiovascular genetic and genomic research," the team wrote. The study, “Association of Transthyretin Val122Ile Variant With Incident Heart Failure Among Black Individuals,” was published in JAMA. Hereditary transthyretin amyloidosis (hATTR) is an umbrella term for diseases caused by genetic mutations that lead to the accumulation of an abnormal version of the transthyretin protein. The faulty transthyretin protein clumps together, forming amyloid fibrils in several tissues, including the nerves, heart, and kidneys. These fibrils can disrupt kidney and heart function. FAP is a type of hATTR in which the peripheral nerves — those found outside the brain and spinal cord — are affected. This particular mutation in TTR was previously found to be associated with transthyretin buildup in the heart, leading to cardiomyopathy. A disease of the heart’s muscle, cardiomyopathy makes it more difficult for the heart to pump blood effectively. The Val122Ile mutation is more common among Black individuals, and may contribute to the increased risk of heart failure observed in the Black community, the researchers noted. To learn more, the team now evaluated the association between Val122Ile and heart failure among 7,514 self-identified Black individuals in the U.S. All are participants in the ongoing Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. The participants had a median age of 64, and 61% were female. Genetic testing revealed the Val122Ile variant was present in 232 participants or 3.1%. If the observed frequency of the variant in this study were generalized to the entire U.S. population, it would suggest that about 1.4 million Black individuals carry it, the researchers wrote. Importantly, however, the team noted that participants in REGARDS were predominately recruited from particular geographic areas; thus, the finding may not be applicable to the entire U.S. population. During a median follow-up of 11.1 years, heart failure occurred in 535 people, 34 of whom carried the Val122Ile variant. A statistical analysis also showed variant carriers were more than two times more likely to experience heart failure compared with noncarriers, suggesting an increased risk of heart failure in the presence of Val122Ile. Overall, deaths were reported in 100 variant carriers and 2,615 noncarriers. Death specifically due to heart failure occurred in 13 variant carriers and 128 noncarriers. Death due to other cardiovascular events occurred in 34 Val122Ile carriers and 759 people without the variant. The risk of death in general, and specifically due to heart failure or cardiovascular causes, were each found to be increased in variant carriers. According to researchers, without treatment, the median survival time of cardiomyopathy associated with hATTR is 2.5 years. Early screening and genetic testing may allow for the condition to be identified and treated more rapidly. “Appropriate diagnostic imaging and testing combined with genetic screening, especially in those with a relevant family history, may allow for early detection of Black individuals at a higher risk of heart failure and death,” they wrote. Future studies including cardiac imaging might enable disease progression to be more closely monitored and definitive diagnoses of hATTR to be made, the team noted. While the findings support a role of Val122Ile in contributing to heart failure and death in the Black community, the team noted that it is only one of several contributing factors. They added that the risk may “predominantly result from adverse environmental factors (lifestyle and clinical factors, systemic racism, and social determinants of health).” Nonetheless, the team called for more inclusion of participants from varying racial and ethnic groups in cardiovascular research generally, and in genetic and genomic studies specifically.

Lindsey Shapiro, PhD, science writer —

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