Prevalence and Phenotype of Transthyretin Val122Ile Variant in the Hispanic Community Health Study/Study of Latinos

Prevalence and Phenotype of Transthyretin Val122Ile Variant in the Hispanic Community Health Study/Study of Latinos

Background: Hereditary transthyretin amyloid cardiomyopathy is commonly caused by the Val122Ile variant, a mutation found in non-Hispanic individuals of West African descent but understudied among the Hispanic/Latino (H/L) population, despite their admixed genetic ancestry (African ancestry [AA], Eu...

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Main Authors: Priscilla Duran-Luciano, MD, Ambarish Pandey, MD, Katrina Swett, MS, Gregory A. Talavera, MD, MPH, Martha Daviglus, MD, PhD, MPH, Barry E. Hurwitz, PhD, Sanjiv J. Shah, MD, Tamar Sofer, PhD, Scott D. Solomon, MD, Susan Cheng, MD, MPH, Larissa Aviles-Santa, MD, MPH, Humberto Parada, Jr., PhD, Bharat Thyagarajan, MD, PhD, MPH, Franklyn Gonzalez, II, MS, Mayank M. Kansal, MD, James Tauras, MD, Mathew S. Maurer, MD, Carlos J. Rodriguez, MD, MPH
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:JACC: Advances
Subjects:
amyloidosis
cardiomyopathies
cohort studies
epidemiology
Hispanic/Latino
Online Access:http://www.sciencedirect.com/science/article/pii/S2772963X25004582
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Summary:Background: Hereditary transthyretin amyloid cardiomyopathy is commonly caused by the Val122Ile variant, a mutation found in non-Hispanic individuals of West African descent but understudied among the Hispanic/Latino (H/L) population, despite their admixed genetic ancestry (African ancestry [AA], European ancestry [EA], and Amerindian ancestry) and heterogeneous AA proportions within disaggregated backgrounds. Objectives: This study aimed to determine Val122Ile variant prevalence among community-dwelling H/L adults and disaggregated background groups; to evaluate associations with genetic continental ancestry; and to characterize echocardiographic phenotype. Methods: We analyzed cross-sectional data from 12,687 H/L adults (aged 18-74) in the Hispanic Community Health Study/Study of Latinos cohort (2008-2011), who consented to genome-wide studies and continental ancestry ascertainment. Echocardiograms were analyzed among 6,376 Hispanics/Latinos ≥44 years. Complex survey analysis, logistic regression, and survey weights were employed. Results: In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), 0.82% of H/Ls carried the Val122Ile variant. H/Ls of Dominican descent had the highest Val122Ile variant prevalence (2.60%) compared to other background groups. Even though Val122Ile carriers had a higher fraction of AA than noncarriers (0.38 vs 0.15, P < 0.0001), their highest fraction of continental ancestry was EA (0.42 ± 0.04). A 1% increase in AA raised Val122Ile variant odds by 4% (OR: 1.04; 95% CI: 1.03-1.06), while a 1% increase in EA or Amerindian ancestry lowered the odds by 3% (OR: 0.97; 95% CI: 0.96-0.99) and 2% (OR: 0.98; 95% CI: 0.97-0.99), respectively. No differences were observed in the echocardiographic phenotype of Val122Ile carriers vs noncarriers. Conclusions: The Val122Ile variant prevalence varied depending on AA proportions among H/Ls and was seen more commonly among Dominicans, highlighting opportunities for preventative hereditary transthyretin amyloid cardiomyopathy screening.
ISSN:2772-963X

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