Duran-Luciano Priscilla, Pandey Ambarish, Swett Katrina, Talavera Gregory A, Daviglus Martha, Hurwitz Barry E, Shah Sanjiv J, Sofer Tamar, Solomon Scott D, Cheng Susan, Aviles-Santa Larissa, Parada Humberto, Thyagarajan Bharat, Gonzalez Franklyn, Kansal Mayank M, Tauras James, Maurer Mathew S, Rodriguez Carlos J
Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA.
UT Southwestern Medical Center, Dallas, Texas, USA.
JACC Adv. 2025 Jul 25;4(8):102034. doi: 10.1016/j.jacadv.2025.102034.
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.
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.
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.
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.
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.
遗传性转甲状腺素蛋白淀粉样心肌病通常由Val122Ile变异引起，该突变在西非裔非西班牙裔个体中发现，但在西班牙裔/拉丁裔（H/L）人群中研究较少，尽管他们具有混合的遗传血统（非洲血统[AA]、欧洲血统[EA]和美洲印第安血统），且在不同背景下AA比例存在差异。
本研究旨在确定社区居住的H/L成年人及不同背景组中Val122Ile变异的患病率；评估与遗传大陆血统的关联；并描述超声心动图表型。
我们分析了西班牙裔社区健康研究/拉丁裔研究队列（2008 - 2011年）中12,687名H/L成年人（年龄18 - 74岁）的横断面数据，这些人同意进行全基因组研究和大陆血统确定。对6,376名年龄≥44岁的西班牙裔/拉丁裔进行了超声心动图分析。采用复杂的调查分析、逻辑回归和调查权重。
在西班牙裔社区健康研究/拉丁裔研究中，0.82%的H/L携带Val122Ile变异。与其他背景组相比，多米尼加裔H/L的Val122Ile变异患病率最高（2.60%）。尽管Val122Ile携带者的AA比例高于非携带者（0.38对0.15，P < 0.0001），但他们的大陆血统中EA比例最高（0.42±0.04）。AA增加1%使Val122Ile变异几率增加4%（OR：1.04；95%CI：1.03 - 1.06），而EA或美洲印第安血统增加1%分别使几率降低3%（OR：0.97；95%CI：0.96 - 0.99）和2%（OR：0.98；95%CI：0.97 - 0.99）。Val122Ile携带者与非携带者的超声心动图表型未观察到差异。
Val122Ile变异患病率因H/L人群中的AA比例而异，在多米尼加人中更为常见，突出了预防性遗传性转甲状腺素蛋白淀粉样心肌病筛查的机会。
