TTR Gene Variant Ups Risk of Heart Failure Among Black Individuals

By Reuters Staff

April 06, 2022

NEW YORK (Reuters Health) - The risk of heart failure is increased in Black carriers of the transthyretin (TTR) Val122Ile mutation, the genetic basis of hereditary transthyretin amyloidosis cardiomyopathy (hATTR-CM), a new study shows.

"Although the study findings indicate a robust association of the TTR Val122Ile variant with incident heart failure, it is unlikely to account for much of the excess heart failure risk experienced by Black individuals," the authors caution in their JAMA paper.

"The TTR Val122Ile variant may only partly contribute to the relatively higher prevalence of heart failure among Black individuals, which may predominantly result from adverse environmental factors (lifestyle and clinical factors, systemic racism, and social determinants of health)," they write.

Dr. Pankaj Arora of the University of Alabama Birmingham and colleagues sought to quantify the association of the TTR Val122Ile variant with incident heart failure and mortality in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

They analyzed data for 7,514 Black participants (median age, 64; 61% women) who had genetic data available and no evidence of heart failure at baseline.

The population frequency of the TTR Val122Ile variant was 3.1%.

During a median follow-up of 11 years, 535 participants developed heart failure. The incidence of heart failure (per 1,000 person-years) was 15.6 in TTR Val122Ile variant carriers compared with 7.16 in noncarriers, yielding an adjusted hazard ratio of 2.43 (P<0.001).

Death due to heart failure, cardiovascular causes, and all causes were all significantly elevated in TTR Val122Ile mutation carriers.

The co-authors of an editorial say the results of this "important study clearly implicate the TTR Val122Ile mutation as a significant risk factor for heart failure among people aged 60 years or older of African descent living in the U.S."

Dr. Melvin Echols and Dr. Herman Taylor with Morehouse School of Medicine in Atlanta note that the population frequency of roughly 3% for this mutation is in line with several prior reports of prevalence rates of 3% to 4% from other cohorts.

"Taken together, these studies imply that the TTR Val122Ile risk allele is a clinically important mutation and routine screening for it is reasonable among Black adults with heart failure," they write.

However, widespread screening (e.g., of asymptomatic family members) beyond cases of unexplained left ventricular hypertrophy or left ventricular functional abnormalities "must be carefully considered given the uncertain aspects of TTR Val122Ile penetrance and expressivity. Genetic counseling consultation may prove helpful in supporting joint patient- physician decision-making for relatives of known clinical cases, carriers of the risk allele, or both," the editorial writers say.

SOURCE: and JAMA, online April 4, 2022.