美国宾夕法尼亚大学Scott M. Damrauer联合西奈山伊坎医学院Ron Do研究组的一项最新研究提出了在非洲或西班牙/拉丁美洲血统的个体中，V122I遗传性淀粉样变性基因变异与心力衰竭的关系。该项研究成果发表在2019年12月10日出版的《美国医学会杂志》上。
为探讨TTR V122I变异与心力衰竭的关系，明确心力衰竭携带者hATTR-CM的诊断率，研究组分析了1996-2017年的电子健康记录数据，对非洲裔TTR V122I携带者和非携带者进行横断面分析，对有心力衰竭和无心力衰竭的非洲裔和西班牙/拉美裔参与者进行病例对照研究。
横断面队列包括3724名非洲裔参与者，平均年龄64岁，2896名（78%）患高血压，753名（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%），心力衰竭1121例（30%）。病例对照研究包括2307名非洲裔和3663名西班牙/拉美裔参与者，中位年龄73岁，4709名（79%）患高血压，1008名（17%）有心肌梗死或冠脉再重建史，心力衰竭1376例。TTR V122I携带者心力衰竭的发生率为44%，显著高于非携带者（30%）。92例TTR V122I携带者中有10例（11%）被诊断为hATTR-CM，从出现症状到确诊平均3年。
Title: Association of the V122I Hereditary Transthyretin Amyloidosis Genetic Variant With Heart Failure Among Individuals of African or Hispanic/Latino Ancestry
Author: Scott M. Damrauer, Kumardeep Chaudhary, Judy H. Cho, Lusha W. Liang, Edgar Argulian, Lili Chan, Amanda Dobbyn, Marie A. Guerraty, Renae Judy, Jenna Kay, Rachel L. Kember, Michael G. Levin, Aparna Saha, Tielman Van Vleck, Shefali S. Verma, JoEllen Weaver, Noura S. Abul-Husn, Aris Baras, Julio A. Chirinos, Brian Drachman, Eimear E. Kenny, Ruth J. F. Loos, Jagat Narula, John Overton, Jeffrey Reid, Marylyn Ritchie, Giorgio Sirugo, Girish Nadkarni, Daniel J. Rader, Ron Do
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.