Association of Val122Ile TTR Variant and HF in Black Individuals

Val122Ile is a genetic variant in the transthyretin (TTR) gene, more common in individuals with African ancestry (3%-4%), and it results in hereditary transthyretin amyloidosis. Researchers conducted a retrospective, population-based study to investigate the association of the amyloidogenic Val122Ile TTR variant with the risk of developing heart failure (HF) and mortality in a robust, geographically diverse cohort of black individuals.

To be eligible, participants had to self-identify as black, live in the United States, participate in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study with genetic data available, and be without HF at baseline; participants were enrolled between 2003 and 2007. The end of follow-up for most outcomes was December 31, 2018, with all-cause mortality data available through 2020. The primary outcome was incident HF (first hospitalization for HF or death due to HF). Secondary outcomes included HF mortality, cardiovascular (CV) mortality, and all-cause mortality.

Of the 7514 black participants, the median age was 64 years, and women represented 61% of the study population. In total, 232 (3.1%) participants were carriers of the Val122Ile TTR variant and 7282 participants were not carriers. During a median follow-up of 11.1 years, incident HF occurred in 34 variant carriers and 501 noncarriers, and the incidence of HF was 15.64 per 1000 person-years in variant carriers versus 7.16 per 1000 person-years in noncarriers (P <.001). In addition, 13 carriers and 128 noncarriers died from HF, and the incidence of HF mortality was 6.11 per 1000 person-years versus 1.85 per 1000 person-years, respectively (P <.001). Statistically significant differences were seen in the incidence of CV death (P = .003) and all-cause mortality (P <.001), both favoring noncarriers.


Parcha V, Malla G, Irvin MR, et al. Association of transthyretin Val122Ile variant with incident heart failure among black individuals. JAMA. 2022;327(14):1368-1378.

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