Importance Hereditary transthyretin (TTR) amyloid cardiomyopathy (hATTR-CM) due to the TTR V122I variant is an autosomal-dominant disorder that causes heart failure in elderly individuals of African ancestry. The clinical associations of carrying the variant, its effect in other African ancestry populations including Hispanic/Latino individuals, and the rates of achieving a clinical diagnosis in carriers are unknown. Objective To assess the association between the TTR V122I variant and heart failure and identify rates of hATTR-CM diagnosis among carriers with heart failure. Design, Setting, and Participants Cross-sectional analysis of carriers and noncarriers of TTR V122I of African ancestry aged 50 years or older enrolled in the Penn Medicine Biobank between 2008 and 2017 using electronic health record data from 1996 to 2017. Case-control study in participants of African and Hispanic/Latino ancestry with and without heart failure in the Mount Sinai BioMe Biobank enrolled between 2007 and 2015 using electronic health record data from 2007 to 2018. Exposures TTR V122I carrier status. Main Outcomes and Measures The primary outcome was prevalent heart failure. The rate of diagnosis with hATTR-CM among TTR V122I carriers with heart failure was measured. Results The cross-sectional cohort included 3724 individuals of African ancestry with a median age of 64 years (interquartile range, 57-71); 1755 (47%) were male, 2896 (78%) had a diagnosis of hypertension, and 753 (20%) had a history of myocardial infarction or coronary revascularization. There were 116 TTR V122I carriers (3.1%); 1121 participants (30%) had heart failure. The case-control study consisted of 2307 individuals of African ancestry and 3663 Hispanic/Latino individuals; the median age was 73 years (interquartile range, 68-80), 2271 (38%) were male, 4709 (79%) had a diagnosis of hypertension, and 1008 (17%) had a history of myocardial infarction or coronary revascularization. There were 1376 cases of heart failure. TTR V122I was associated with higher rates of heart failure (cross-sectional cohort: n = 51/116 TTR V122I carriers [44%], n = 1070/3608 noncarriers [30%], adjusted odds ratio, 1.7 [95% CI, 1.2-2.4], P = .006; case-control study: n = 36/1376 heart failure cases [2.6%], n = 82/4594 controls [1.8%], adjusted odds ratio, 1.8 [95% CI, 1.2-2.7], P = .008). Ten of 92 TTR V122I carriers with heart failure (11%) were diagnosed as having hATTR-CM; the median time from onset of symptoms to clinical diagnosis was 3 years. Conclusions and Relevance Among individuals of African or Hispanic/Latino ancestry enrolled in 2 academic medical center-based biobanks, the TTR V122I genetic variant was significantly associated with heart failure.

中文翻译：

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V122I 遗传性转甲状腺素蛋白淀粉样变性基因变异与非洲或西班牙裔/拉丁裔血统个体心力衰竭的关联

重要性 由 TTR V122I 变异引起的遗传性转甲状腺素蛋白 (TTR) 淀粉样蛋白心肌病 (hATTR-CM) 是一种常染色体显性遗传疾病，可导致非洲血统老年人心力衰竭。携带该变异的临床关联、其对其他非洲血统人群（包括西班牙裔/拉丁裔个体）的影响以及携带者获得临床诊断的比率尚不清楚。目的 评估 TTR V122I 变异与心力衰竭之间的关联，并确定心力衰竭携带者中 hATTR-CM 的诊断率。设计、设置和参与者 使用 1996 年至 2017 年的电子健康记录数据，对 2008 年至 2017 年间加入 Penn Medicine Biobank 的年龄 50 岁或以上的非洲血统 TTR V122I 携带者和非携带者进行横断面分析。使用 2007 年至 2018 年的电子健康记录数据，在 2007 年至 2015 年期间登记了西奈山 BioMe 生物库中患有或不患有心力衰竭的非洲裔和西班牙裔/拉丁裔血统的参与者。暴露了 TTR V122I 携带者状态。主要结果和措施 主要结果是普遍的心力衰竭。测量了患有心力衰竭的 TTR V122I 携带者中 hATTR-CM 的诊断率。结果横断面队列包括 3724 名非洲血统个体，中位年龄为 64 岁（四分位数范围为 57-71 岁）；1755 名（47%）为男性，2896 名（78%）被诊断为高血压，753 名（20%）有心肌梗死或冠状动脉血运重建史。有116个TTR V122I携带者（3.1%）；1121 名参与者 (30%) 患有心力衰竭。病例对照研究由 2307 名非洲裔个体和 3663 名西班牙裔/拉丁裔个体组成；中位年龄为 73 岁（四分位距，68-80），2271 名（38%）为男性，4709 名（79%）被诊断为高血压，1008 名（17%）有心肌梗死或冠状动脉血运重建史。有1376例心力衰竭病例。TTR V122I 与较高的心力衰竭发生率相关（横断面队列：n = 51/116 TTR V122I 携带者 [44%]，n = 1070/3608 非携带者 [30%]，调整后的比值比，1.7 [95% CI， 1.2-2.4]，P = .006；病例对照研究：n = 36/1376 心力衰竭病例 [2.6%]，n = 82/4594 对照 [1.8%]，调整优势比，1.8 [95% CI，1.2 -2.7]，P = .008）。92 名患有心力衰竭的 TTR V122I 携带者中有 10 名 (11%) 被诊断为 hATTR-CM；从出现症状到临床诊断的中位时间为 3 年。结论和相关性 在 2 个学术医疗中心生物库中登记的非洲或西班牙/拉丁裔血统个体中，TTR V122I 遗传变异与心力衰竭显着相关。