Genetic variant linked to HF in people of African American or Latino ancestry
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The TTR V122I genetic variant was significantly linked to HF among patients of African or Latino ancestry, according to a study published in JAMA.
“This study is the first real-world ‘genome-first’ study of TTR V122I linked to health records, and so is not biased by who has been referred for TTR testing,” Daniel J. Rader, MD, chair of the department of genetics, chief of the division of translational medicine and human genetics and the Seymour-Gray Professor of Molecular Medicine at the University of Pennsylvania Perelman School of Medicine, told Healio. “It demonstrates the very substantial underdiagnosis of this very treatable disease even at places like Penn and Mount Sinai.”
Carriers and noncarriers of TTR V122I
Scott M. Damrauer, MD, assistant professor of surgery at University of Pennsylvania Perelman School of Medicine, and colleagues analyzed data from a cross-sectional cohort of 3,724 patients (median age, 64 years; 47% men; 78% diagnosed with hypertension; 20% had a history of MI or coronary revascularization) of African ancestry aged 50 years and older. Patients in this cohort were carriers and noncarriers of TTR V122I and were enrolled in the Penn Medicine BioBank between 2008 and 2017.
A case-control study was also conducted in 2,307 patients (median age, 73 years; 38% men; 79% diagnosed with hypertension; 17% had a history of MI or coronary revascularization) of African and Hispanic/Latino ancestry from the Mount Sinai BioMe BioBank. These patients were with or without HF and were enrolled between 2007 and 2015.
The primary outcome was defined as prevalent HF at the time the data were extracted.
Of the patients in the cross-sectional cohort, 3.1% were carriers of TTR V122I and 30% had HF. There were 1,376 patients with HF in the case-control study.
Compared with noncarriers, patients who carried TTR V122I had higher rates of HF, as shown in the cross-sectional cohort (44% vs. 30%; adjusted OR = 1.7; 95% CI, 1.2-2.4) and the case-control study (2.6% vs. 1.8%; aOR = 1.8; 95% CI, 1.2-2.7).
Of the 92 patients who were carriers of TTR V122I, 11% were diagnosed with hereditary transthyretin amyloid cardiomyopathy with a median time from symptom onset to clinical diagnosis of 3 years.
“Tafamidis (Vyndamax and Vyndaqel; FoldRx/Pfizer) has been shown to be very effective in treating [hereditary transthyretin] amyloid cardiomyopathy and was approved by [the] FDA in May 2019,” Rader said in an interview. “There are too other TTR-targeted therapies approved for TTR neuropathy that are being actively studied for their effects in cardiomyopathy. Physicians need to be much more active in considering the diagnosis of [hereditary transthyretin] amyloid cardiomyopathy and performing appropriate diagnostic evaluation including sequencing of TTR when appropriate.”
Further research
Rader also told Healio that more research is needed in this area. “There is wide variability in the development of heart disease and neuropathy in carriers of TTR V122I. We don’t understand that and need more research. We also need to test whether tafamidis and the other TTR therapies prevent the development of cardiomyopathy and neuropathy rather than waiting for the symptoms to occur,” he said. – by Darlene Dobkowski
For more information:
Daniel J. Rader, MD, can be reached at Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd., 11-125 Smilow Center for Translational Research, Philadelphia, PA 19104; email: rader@pennmedicine.upenn.edu.
Disclosures: Regeneron Genetics Center assisted with the collection, management and analysis of the genetic data. Rader reports he received personal fees from Akcea, Alnylam Pharmaceuticals, Novartis and Pfizer and nonfinancial support from Regeneron Pharmaceuticals. Damrauer reports he received grants from the CytoVas LLC, Renalytix AI and the U.S. Department of Veterans Affairs. Please see the study for all other authors’ relevant financial disclosures.
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