Association of the V122I Hereditary Transthyretin Amyloidosis Genetic Variant With Heart Failure Among Individuals of African or Hispanic/Latino Ancestry
Association of the V122I Hereditary Transthyretin Amyloidosis Genetic Variant With Heart Failure Among Individuals of African or Hispanic/Latino Ancestry
复制标题
DOI：
10.1001/jama.2019.17935
复制
发表时间：
2019-12-10
影响因子：
120.7
通讯作者：
Do, Ron
中科院分区：
文献类型：
--
作者：
Damrauer, Scott M.;Chaudhary, Kumardeep;Do, Ron
由TTR V122I变异引起的遗传性甲状腺素转运蛋白（TTR）淀粉样心肌病（hatr - cm）是一种常染色体显性疾病，可导致非洲血统老年人心力衰竭。携带该变异的临床关联，其在其他非洲血统人群（包括西班牙裔/拉丁裔个体）中的影响，以及在携带者中获得临床诊断的比率尚不清楚。目的评估TTR V122I变异与心力衰竭的关系，并确定心力衰竭携带者中hatr - cm的诊断率。设计、环境和参与者：使用1996年至2017年的电子健康记录数据，对2008年至2017年在宾夕法尼亚大学医学生物银行登记的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。在2007年至2015年期间，西奈山BioMe生物银行中有和没有心力衰竭的非洲和西班牙裔/拉丁裔参与者进行病例对照研究，使用2007年至2018年的电子健康记录数据。暴露TTR V122I载波状态。主要结局和测量主要结局是普遍的心力衰竭。测量TTR V122I携带者心力衰竭患者的hat - cm诊断率。结果横断面队列包括3724名非洲血统的个体，中位年龄为64岁（四分位数范围为57-71）；1755例（47%）为男性，2896例（78%）诊断为高血压，753例（20%）有心肌梗死或冠状动脉血运重建史。TTR V122I携带者116例（3.1%）；1121名参与者（30%）有心力衰竭。病例对照研究包括2307名非洲裔个体和3663名西班牙裔/拉丁裔个体；中位年龄为73岁（四分位数范围为68-80），男性2271人（38%），4709人（79%）诊断为高血压，1008人（17%）有心肌梗死或冠状动脉血管重建术史。有1376例心力衰竭。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%]，校正优势比为1.7 [95% CI, 1.2-2.4], P = 0.006；病例对照研究：n = 36/1376心力衰竭病例[2.6%],n = 82/4594对照组[1.8%]，校正优势比为1.8 [95% CI, 1.2-2.7], P = 0.008）。92例TTR V122I携带者中有10例心衰（11%）被诊断为hatr - 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个学术医学中心生物库中登记的非洲或西班牙/拉丁裔个体中，TTR V122I基因变异与心力衰竭显著相关。
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 outcomewas 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 ofmyocardial 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 ofmyocardial 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.