Clonal hematopoiesis of indeterminate potential (CHIP): Linking somatic mutations, hematopoiesis, chronic inflammation and cardiovascular disease.
Clonal hematopoiesis of indeterminate potential (CHIP): Linking somatic mutations, hematopoiesis, chronic inflammation and cardiovascular disease.
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DOI：
10.1016/j.yjmcc.2021.07.004
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发表时间：
2021-12
影响因子：
5
通讯作者：
Natarajan P
中科院分区：
文献类型：
--
作者：
Marnell CS;Bick A;Natarajan P
不确定潜能的克隆性造血（CHIP）是在没有血液学恶性肿瘤、发育不良或血细胞减少的证据的个体中存在由致白血病突变引起的克隆扩增的造血干细胞。CHIP与每年0.5-1.0%的白血病风险相关。值得注意的是，它使心血管风险增加了两倍，与传统的风险因素无关。大约80%的CHIP患者在表观遗传调节因子DNMT 3A、TET 2、ASXL 1、DNA损伤修复基因PPM 1D、TP 53、调节性酪氨酸激酶JAK 2或mRNA剪接体组分SF 3B 1和SRSF 2中存在突变。CHIP与促炎状态相关，促炎状态与冠状动脉疾病、心肌梗死和静脉血栓栓塞性疾病以及主动脉瓣狭窄和心力衰竭患者的预后有关。遗传和获得性风险因素与CHIP患病率增加相关，包括生殖系变异、年龄、不健康的生活方式行为（即吸烟、肥胖）、炎症、过早绝经、HIV和暴露于癌症治疗。本综述旨在总结CHIP的新兴研究，其在传播炎症和加速心血管疾病中的重要作用的机制，以及详细说明增加CHIP患病率的相关风险因素和合并症的新研究。
Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of a clonally expanded hematopoietic stem cell caused by a leukemogenic mutation in individuals without evidence of hematologic malignancy, dysplasia, or cytopenia. CHIP is associated with a 0.5-1.0% risk per year of leukemia. Remarkably, it confers a two-fold increase in cardiovascular risk independent of traditional risk factors. Roughly 80% of patients with CHIP have mutations in epigenetic regulators DNMT3A, TET2, ASXL1, DNA damage repair genes PPM1D, TP53, the regulatory tyrosine kinase JAK2, or mRNA spliceosome components SF3B1, and SRSF2. CHIP is associated with a pro-inflammatory state that has been linked to coronary artery disease, myocardial infarction, and venous thromboembolic disease, as well as prognosis among those with aortic stenosis and heart failure. Heritable and acquired risk factors are associated with increased CHIP prevalence, including germline variation, age, unhealthy lifestyle behaviors (i.e. smoking, obesity), inflammatory conditions, premature menopause, HIV and exposure to cancer therapies. This review aims to summarize emerging research on CHIP, the mechanisms underlying its important role in propagating inflammation and accelerating cardiovascular disease, and new studies detailing the role of associated risk factors and co-morbidities that increase CHIP prevalence.
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影响因子：
64.8
作者：
Bick AG;Weinstock JS;Nandakumar SK;Fulco CP;Bao EL;Zekavat SM;Szeto MD;Liao X;Leventhal MJ;Nasser J;Chang K;Laurie C;Burugula BB;Gibson CJ;Lin AE;Taub MA;Aguet F;Ardlie K;Mitchell BD;Barnes KC;Moscati A;Fornage M;Redline S;Psaty BM;Silverman EK;Weiss ST;Palmer ND;Vasan RS;Burchard EG;Kardia SLR;He J;Kaplan RC;Smith NL;Arnett DK;Schwartz DA;Correa A;de Andrade M;Guo X;Konkle BA;Custer B;Peralta JM;Gui H;Meyers DA;McGarvey ST;Chen IY;Shoemaker MB;Peyser PA;Broome JG;Gogarten SM;Wang FF;Wong Q;Montasser ME;Daya M;Kenny EE;North KE;Launer LJ;Cade BE;Bis JC;Cho MH;Lasky-Su J;Bowden DW;Cupples LA;Mak ACY;Becker LC;Smith JA;Kelly TN;Aslibekyan S;Heckbert SR;Tiwari HK;Yang IV;Heit JA;Lubitz SA;Johnsen JM;Curran JE;Wenzel SE;Weeks DE;Rao DC;Darbar D;Moon JY;Tracy RP;Buth EJ;Rafaels N;Loos RJF;Durda P;Liu Y;Hou L;Lee J;Kachroo P;Freedman BI;Levy D;Bielak LF;Hixson JE;Floyd JS;Whitsel EA;Ellinor PT;Irvin MR;Fingerlin TE;Raffield LM;Armasu SM;Wheeler MM;Sabino EC;Blangero J;Williams LK;Levy BD;Sheu WH;Roden DM;Boerwinkle E;Manson JE;Mathias RA;Desai P;Taylor KD;Johnson AD;NHLBI Trans-Omics for Precision Medicine Consortium;Auer PL;Kooperberg C;Laurie CC;Blackwell TW;Smith AV;Zhao H;Lange E;Lange L;Rich SS;Rotter JI;Wilson JG;Scheet P;Kitzman JO;Lander ES;Engreitz JM;Ebert BL;Reiner AP;Jaiswal S;Abecasis G;Sankaran VG;Kathiresan S;Natarajan P
通讯作者：
Natarajan P
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
11.4
作者：
Dawoud, Ahmed A. Z.;Tapper, William J.;Cross, Nicholas C. P.
通讯作者：
Cross, Nicholas C. P.
影响因子：
20.3
作者：
Buscarlet, Manuel;Provost, Sylvie;Busque, Lambert
通讯作者：
Busque, Lambert
影响因子：
5.4
作者：
Haring B;Reiner AP;Liu J;Tobias DK;Whitsel E;Berger JS;Desai P;Wassertheil-Smoller S;LaMonte MJ;Hayden KM;Bick AG;Natarajan P;Weinstock JS;Nguyen PK;Stefanick M;Simon MS;Eaton CB;Kooperberg C;Manson JE
通讯作者：
Manson JE