Association of Transthyretin Val122Ile Variant With Incident Heart Failure Among Black Individuals

Abstract

Key PointsQuestionsWhat is the association between amyloidogenic TTR gene variation (Val122Ile) and the risk of heart failure?FindingsIn this retrospective cohort study that included 7514 Black participants in the US with a median 11.1 years of follow-up, the incidence of heart failure was 15.6 per 1000 person-years among Val122Ile variant carriers compared with 7.2 per 1000 person-years among noncarriers, with an adjusted hazard ratio of 2.43.MeaningBeing a carrier of the Val122Ile variant was significantly associated with an increased risk of heart failure among Black individuals living in the US.

In silico analysis decodes transthyretin (TTR) binding and thyroid disrupting effects of per- and polyfluoroalkyl substances (PFAS)

“…Behavior, cognition, neuropeptide amidation, neurogenesis, nerve regeneration, and axonal growth are some of the cellular processes where TTR has an important role (Vieira and Saraiva 2014 ). Further, mutations in the TTR gene are implicated in the etiology of several diseases, including amyloidotic polyneuropathy, euthyroid hyperthyroxinaemia, amyloidotic vitreous opacities, cardiomyopathy, oculoleptomeningeal amyloidosis, meningocerebrovascular amyloidosis, and carpal tunnel syndrome (Bekircan-Kurt et al 2022 ; Coniglio et al 2022 ; Parcha et al 2022 ; Takahashi et al 2022 ; Yee et al 2019 ). Besides, maternal exposure to PFASs can result in serum concentration of PFASs in fetuses and newborns, which leads to hypothyroidism, slow growth and development, and mental retardation as explained in Fig.…”

Incorrect Spelling of Author Name

“…In the Original Investigation titled “Association of Transthyretin Val122Ile Variant With Incident Heart Failure Among Black Individuals,” published in the April 12, 2022, issue of JAMA , an author name was misspelled. In the byline, the third author, “Marguerite R. Ivin, PhD” should have been “Marguerite R. Irvin, PhD.” This article was corrected online.…”

Heart Failure, Precision Medicine, and Incremental Equity

“…In this issue of JAMA , Parcha et al add to the growing literature on the risk of heart failure associated with the TTR Val122Ile mutation, the genetic basis of hereditary transthyretin amyloidosis cardiomyopathy (hATTR-CM). This report on the outcomes associated with heritable, amyloid-related heart failure is particularly timely.…”

“…Parcha et al 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, which includes a large, geographically diverse cohort of Black individuals. The investigators analyzed data from 7514 self-identified Black participants who had genetic data available and no evidence of heart failure at baseline.…”

“…Furthermore, as with other major health disparities, even though huge investments in research and development have produced greater mechanistic insight and an ever-widening therapeutic armamentarium, thereby improving outcomes for patients with heart failure in general, they have not produced a substantial reduction in race-related disparities . As Parcha et al suggest, initiatives that massively expand screening for TTR Val122Ile should not be expected to have a substantial effect on the persistent disparity between Black and White individuals with heart failure in the US.…”