The amyloidogenic V122I transthyretin variant in elderly black Americans.

TitleThe amyloidogenic V122I transthyretin variant in elderly black Americans.
Publication TypeJournal Article
Year of Publication2015
AuthorsC Quarta, C, Buxbaum, JN, Shah, AM, Falk, RH, Claggett, B, Kitzman, DW, Mosley, TH, Butler, KR, Boerwinkle, E, Solomon, SD
JournalN Engl J Med
Date Published2015 Jan 1
KeywordsAfrican Americans, Aged, Amyloidosis, Cardiomyopathy, Restrictive, Cohort Studies, Echocardiography, Female, Follow-Up Studies, Genotype, Heart Failure, Heterozygote, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Prealbumin

BACKGROUND: Approximately 4% of black Americans carry a valine-to-isoleucine substitution (V122I) in the transthyretin protein, which has been associated with late-onset restrictive amyloid cardiomyopathy and increased risks of death and heart failure.

METHODS: We determined genotype status for the transthyretin gene (TTR) in 3856 black participants in the Atherosclerosis Risk in Communities study and assessed clinical profiles, mortality, and the risk of incident heart failure in V122I TTR variant carriers (124 participants [3%]) versus noncarriers (3732 participants). Cardiac structure and function and features suggestive of cardiac amyloidosis were assessed in participants who underwent echocardiography during visit 5 (2011 to 2013), when they were older than 65 years of age.

RESULTS: After 21.5 years of follow-up, we did not detect a significant difference in mortality between carriers (41 deaths, 33%) and noncarriers (1382 deaths, 37%; age- and sex-stratified hazard ratio among carriers, 0.99; 95% confidence interval [CI], 0.73 to 1.36; P=0.97). The TTR variant was associated with an increased risk of incident heart failure (age- and sex-stratified hazard ratio, 1.47; 95% CI, 1.03 to 2.10; P=0.04). On echocardiography at visit 5, carriers (46 participants) had worse systolic and diastolic function, as well as a higher level of N-terminal pro-brain natriuretic peptide, than noncarriers (1194 participants), although carriers had a low prevalence (7%) of overt manifestations of amyloid cardiomyopathy.

CONCLUSIONS: We did not detect a significant difference in mortality between V122I TTR allele carriers and noncarriers, a finding that contrasts with prior observations; however, the risk of heart failure was increased among carriers. The prevalence of overt cardiac abnormalities among V122I TTR carriers was low. (Funded by the National Heart, Lung, and Blood Institute and others.).

Alternate JournalN. Engl. J. Med.
PubMed ID25551524
PubMed Central IDPMC4382209
Grant ListHC-11-08 / HC / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100006C / / PHS HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100010C / / PHS HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
P30 AG021332 / AG / NIA NIH HHS / United States
R01 AG018915 / AG / NIA NIH HHS / United States
R01 AG19259 / AG / NIA NIH HHS / United States