Association of the V122I Hereditary Transthyretin Amyloidosis Genetic Variant With Heart Failure Among Individuals of African or Hispanic/Latino Ancestry

被引：106

作者：

Damrauer, Scott M. ^{[1
,2
]}

Chaudhary, Kumardeep ^{[3
,4
,5
]}

Cho, Judy H. ^{[3
,4
,5
,6
]}

Liang, Lusha W. ^{[7
]}

Argulian, Edgar ^{[8
]}

Chan, Lili ^{[3
,4
,6
]}

Dobbyn, Amanda ^{[3
,4
,5
]}

Guerraty, Marie A. ^{[9
]}

Judy, Renae ^{[1
]}

Kay, Jenna ^{[9
]}

Kember, Rachel L. ^{[10
,11
]}

Levin, Michael G. ^{[9
]}

Saha, Aparna ^{[3
,4
]}

Van Vleck, Tielman ^{[3
,4
]}

Verma, Shefali S. ^{[10
]}

Weaver, JoEllen ^{[12
]}

Abul-Husn, Noura S. ^{[3
,5
,6
,13
]}

Baras, Aris ^{[14
]}

Chirinos, Julio A. ^{[9
]}

Drachman, Brian ^{[9
]}

Kenny, Eimear E. ^{[3
,5
,13
]}

Loos, Ruth J. F. ^{[3
,15
,16
]}

Narula, Jagat ^{[8
]}

Overton, John ^{[14
]}

Reid, Jeffrey ^{[14
]}

Ritchie, Marylyn ^{[10
]}

Sirugo, Giorgio ^{[17
]}

Nadkarni, Girish ^{[3
,4
,6
]}

Rader, Daniel J. ^{[7
,10
,17
]}

Do, Ron ^{[3
,4
,5
]}

机构：

[1] Univ Penn, Dept Surg, Perelman Sch Med, Philadelphia, PA 19104 USA

[2] Corporal Michael Crescenz VA Med Ctr, Dept Surg, Philadelphia, PA USA

[3] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA

[4] Icahn Sch Med Mt Sinai, BioMe Phen Ctr, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA

[7] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA

[8] Icahn Sch Med Mt Sinai, Mt Sinai Heart, New York, NY 10029 USA

[9] Univ Penn, Dept Med, Perelman Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA

[10] Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA

[11] Corporal Michael Crescenz VA Med Ctr, MIRECC, Philadelphia, PA USA

[12] Univ Penn, Inst Translat Med & Therapeut, Perelman Sch Med, Philadelphia, PA 19104 USA

[13] Icahn Sch Med Mt Sinai, Ctr Genom Hlth, New York, NY 10029 USA

[14] Regeneron Genet Ctr, Tarrytown, NY USA

[15] Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA

[16] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA

[17] Univ Penn, Dept Med, Div Translat Med & Human Genet, Perelman Sch Med, Philadelphia, PA 19104 USA

来源：

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2019年 / 322卷 / 22期

基金：

美国国家卫生研究院;

关键词：

CARDIAC AMYLOIDOSIS; ALLELE; PREVALENCE; AMERICANS; CARDIOMYOPATHY; PHENOTYPE;

D O I：

10.1001/jama.2019.17935

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2191 / 2202

页数：12

共 29 条

[1] Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis [J].

Adams, D. ;

Gonzalez-Duarte, A. ;

O'Riordan, W. D. ;

Yang, C. -C. ;

Ueda, M. ;

Kristen, A. V. ;

Tournev, I. ;

Schmidt, H. H. ;

Coelho, T. ;

Berk, J. L. ;

Lin, K. -P. ;

Vita, G. ;

Attarian, S. ;

Plante-Bordeneuve, V. ;

Mezei, M. M. ;

Campistol, J. M. ;

Buades, J. ;

Brannagan, T. H., III ;

Kim, B. J. ;

Oh, J. ;

Parman, Y. ;

Sekijima, Y. ;

Hawkins, P. N. ;

Solomon, S. D. ;

Polydefkis, M. ;

Dyck, P. J. ;

Gandhi, P. J. ;

Goyal, S. ;

Chen, J. ;

Strahs, A. L. ;

Nochur, S. V. ;

Sweetser, M. T. ;

Garg, P. P. ;

Vaishnaw, A. K. ;

Gollob, J. A. ;

Suhr, O. B. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (01) :11-21

[2] Statistics Notes - Interaction revisited: the difference between two estimates [J].

Altman, DG ;

Bland, JM .

BMJ-BRITISH MEDICAL JOURNAL, 2003, 326 (7382) :219-219

[3]

[Anonymous], 2017, R LANG ENV STAT COMP

[4] Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis [J].

Benson, M. D. ;

Waddington-Cruz, M. ;

Berk, J. L. ;

Polydefkis, M. ;

Dyck, P. J. ;

Wang, A. K. ;

Plante-Bordeneuve, V. ;

Barroso, F. A. ;

Merlini, G. ;

Obici, L. ;

Scheinberg, M. ;

Brannagan, T. H., III ;

Litchy, W. J. ;

Whelan, C. ;

Drachman, B. M. ;

Adams, D. ;

Heitner, S. B. ;

Conceicao, I. ;

Schmidt, H. H. ;

Vita, G. ;

Campistol, J. M. ;

Gamez, J. ;

Gorevic, P. D. ;

Gane, E. ;

Shah, A. M. ;

Solomon, S. D. ;

Monia, B. P. ;

Hughes, S. G. ;

Kwoh, T. J. ;

McEvoy, B. W. ;

Jung, S. W. ;

Baker, B. F. ;

Ackermann, E. J. ;

Gertz, M. A. ;

Coelho, T. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (01) :22-31

[5] The Genetic Ancestry of African Americans, Latinos, and European Americans across the United States [J].

Bryc, Katarzyna ;

Durand, Eric Y. ;

Macpherson, J. Michael ;

Reich, David ;

Mountain, Joanna L. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2015, 96 (01) :37-53

[6] Transthyretin V122I in African Americans with congestive heart failure [J].

Buxbaum, J ;

Jacobson, DR ;

Tagoe, C ;

Alexander, A ;

Kitzman, DW ;

Greenberg, B ;

Thaneemit-Chen, S ;

Lavori, P .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2006, 47 (08) :1724-1725

[7] Significance of the amyloidogenic transthyretin Val 122 Ile allele in African Americans in the Arteriosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies [J].

Buxbaum, Joel ;

Alexander, Alice ;

Koziol, James ;

Tagoe, Clement ;

Fox, Ervin ;

Kitzman, Dalane .

AMERICAN HEART JOURNAL, 2010, 159 (05) :864-870

[8] Transthyretin V122I ( pV142I)* cardiac amyloidosis: an age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans [J].

Buxbaum, Joel N. ;

Ruberg, Frederick L. .

GENETICS IN MEDICINE, 2017, 19 (07) :733-742

[9] Second-generation PLINK: rising to the challenge of larger and richer datasets [J].

Chang, Christopher C. ;

Chow, Carson C. ;

Tellier, Laurent C. A. M. ;

Vattikuti, Shashaank ;

Purcell, Shaun M. ;

Lee, James J. .

GIGASCIENCE, 2015, 4

[10] Genetic Diversity and Association Studies in US Hispanic/Latino Populations: Applications in the Hispanic Community Health Study/Study of Latinos [J].

Conomos, Matthew P. ;

Laurie, Cecelia A. ;

Stilp, Adrienne M. ;

Gogarten, Stephanie M. ;

McHugh, Caitlin P. ;

Nelson, Sarah C. ;

Sofer, Tamar ;

Fernandez-Rhodes, Lindsay ;

Justice, Anne E. ;

Graff, Mariaelisa ;

Young, Kristin L. ;

Seyerle, Amanda A. ;

Avery, Christy L. ;

Taylor, Kent D. ;

Rotter, Jerome I. ;

Talavera, Gregory A. ;

Daviglus, Martha L. ;

Wassertheil-Smoller, Sylvia ;

Schneiderman, Neil ;

Heiss, Gerardo ;

Kaplan, Robert C. ;

Franceschini, Nora ;

Reiner, Alex P. ;

Shaffer, John R. ;

Barr, R. Graham ;

Kerr, Kathleen F. ;

Browning, Sharon R. ;

Browning, Brian L. ;

Weir, Bruce S. ;

Aviles-Santa, M. Larissa ;

Papanicolaou, George J. ;

Lumley, Thomas ;

Szpiro, Adam A. ;

North, Kari E. ;

Rice, Ken ;

Thornton, Timothy A. ;

Laurie, Cathy C. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2016, 98 (01) :165-184

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