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Clonal Hematopoiesi...
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Jaiswal, SiddharthaBrigham and Women's Hospital / Harvard Medical School
(författare)
Clonal Hematopoiesis and risk of atherosclerotic cardiovascular disease
- Artikel/kapitelEngelska2017
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Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:dda178ce-b7e6-4c2c-9126-16625aa896d5
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https://lup.lub.lu.se/record/dda178ce-b7e6-4c2c-9126-16625aa896d5URI
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https://doi.org/10.1056/NEJMoa1701719DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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BACKGROUND Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among older persons and is associated with an increased risk of hematologic cancer. We previously found preliminary evidence for an association between CHIP and atherosclerotic cardiovascular disease, but the nature of this association was unclear. METHODS We used whole-exome sequencing to detect the presence of CHIP in peripheral-blood cells and associated such presence with coronary heart disease using samples from four case-control studies that together enrolled 4726 participants with coronary heart disease and 3529 controls. To assess causality, we perturbed the function of Tet2, the second most commonly mutated gene linked to clonal hematopoiesis, in the hematopoietic cells of atherosclerosis-prone mice. RESULTS In nested case-control analyses from two prospective cohorts, carriers of CHIP had a risk of coronary heart disease that was 1.9 times as great as in noncarriers (95% confidence interval [CI], 1.4 to 2.7). In two retrospective case-control cohorts for the evaluation of early-onset myocardial infarction, participants with CHIP had a risk of myocardial infarction that was 4.0 times as great as in noncarriers (95% CI, 2.4 to 6.7). Mutations in DNMT3A, TET2, ASXL1, and JAK2 were each individually associated with coronary heart disease. CHIP carriers with these mutations also had increased coronary-artery calcification, a marker of coronary atherosclerosis burden. Hypercholesterolemia-prone mice that were engrafted with bone marrow obtained from homozygous or heterozygous Tet2 knockout mice had larger atherosclerotic lesions in the aortic root and aorta than did mice that had received control bone marrow. Analyses of macrophages from Tet2 knockout mice showed elevated expression of several chemokine and cytokine genes that contribute to atherosclerosis. CONCLUSIONS The presence of CHIP in peripheral-blood cells was associated with nearly a doubling in the risk of coronary heart disease in humans and with accelerated atherosclerosis in mice. (Funded by the National Institutes of Health and others.)
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Natarajan, PMassachusetts General Hospital,Massachusetts Institute of Technology,Parma University Hospital
(författare)
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Silver, A. J.Brigham and Women's Hospital / Harvard Medical School
(författare)
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Gibson, C. J.Parma University Hospital,Massachusetts Institute of Technology
(författare)
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Bick, Alexander G.Massachusetts General Hospital
(författare)
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Shvartz, E.Brigham and Women's Hospital / Harvard Medical School
(författare)
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McConkey, Marie E.Brigham and Women's Hospital / Harvard Medical School
(författare)
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Gupta, NLund University
(författare)
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Gabriel, R. S.Parma University Hospital,Massachusetts Institute of Technology
(författare)
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Ardissino, DiegoIcahn School of Medicine at Mount Sinai
(författare)
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Baber, UsmanLund University
(författare)
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Mehran, RoxanaMayo Clinic Minnesota
(författare)
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Fuster, VCentro Nacional de Investigaciones Cardiovasculares Carlos III,British Heart Foundation
(författare)
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Danesh, J.University of Cambridge
(författare)
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Frossard, PCenter for Non-Communicable Diseases,Wellcome Trust
(författare)
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Saleheen, D.Lund University
(författare)
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Melander, O.Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,University of Pennsylvania,Harvard Medical School(Swepub:lu)endo-ome
(författare)
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Sukhova, Galina KMayo Clinic Minnesota
(författare)
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Neuberg, DonnaDana-Farber Cancer Institute
(författare)
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Libby, PMayo Clinic Minnesota
(författare)
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Kathiresan, S.Parma University Hospital,Massachusetts Institute of Technology,Massachusetts General Hospital,University of Cincinnati
(författare)
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Ebert, Benjamin L.Brigham and Women's Hospital / Harvard Medical School
(författare)
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Brigham and Women's Hospital / Harvard Medical SchoolMassachusetts General Hospital
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:New England Journal of Medicine377:2, s. 111-1210028-4793
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Till lärosätets databas
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Jaiswal, Siddhar ...
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Natarajan, P
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Silver, A. J.
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Gibson, C. J.
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Bick, Alexander ...
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Shvartz, E.
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visa fler...
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McConkey, Marie ...
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Gupta, N
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Gabriel, R. S.
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Ardissino, Diego
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Baber, Usman
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Mehran, Roxana
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Fuster, V
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Danesh, J.
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Frossard, P
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Saleheen, D.
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Melander, O.
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Sukhova, Galina ...
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Neuberg, Donna
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Libby, P
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Kathiresan, S.
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Ebert, Benjamin ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
- Artiklar i publikationen
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New England Jour ...
- Av lärosätet
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Lunds universitet