Genetic and pharmacologic inactivation of ANGPTL3 and cardiovascular disease

New England Journal of Medicine

Volumn 377, Issue 3, 2017, Pages 211-221

  Dewey, Frederick E ^a   Gusarova, Viktoria ^b   Dunbar, Richard L ^c   O'Dushlaine, Colm ^a   Schurmann, Claudia ^a   Gottesman, Omri ^a   McCarthy, Shane ^a   Van Hout, Cristopher V ^a   Bruse, Shannon ^a   Dansky, Hayes M ^b   Leader, Joseph B ^e   Murray, Michael F ^e   Ritchie, Marylyn D ^e   Kirchner, H Lester ^e   Habegger, Lukas ^a   Lopez, Alex ^a   Penn, John ^a   Zhao, An ^b   Shao, Weiping ^b   Stahl, Neil ^a,b   Murphy, Andrew J ^a,b   Hamon, Sara ^b   Bouzelmat, Aurelie ^b   Zhang, Rick ^b   Shumel, Brad ^b   Pordy, Robert ^b   Gipe, Daniel ^b   Herman, Gary A ^b   Sheu, Wayne H H ^f,h,k,l   Lee, I Te ^f,i,k   Liang, Kae Woei ^g,j,k   Guo, Xiuqing ^m   Rotter, Jerome I ^m   Chen, Yii Der I ^m   Kraus, William E ⁿ   Shah, Svati H ⁿ   Damrauer, Scott ^c   Small, Aeron ^d   Rader, Daniel J ^d   Wulff, Anders Berg ^o   Nordestgaard, Børge G ^o,p,q,r   Tybjærg Hansen, Anne ^o,p,r   Van Den Hoek, Anita M ^s   Princen, Hans M G ^s   Ledbetter, David H ^e   Carey, David J ^e   Overton, John D ^a   Reid, Jeffrey G ^a   Sasiela, William J ^b   Banerjee, Poulabi ^b   Shuldiner, Alan R ^a   Borecki, Ingrid B ^a   Teslovich, Tanya M ^a   Yancopoulos, George D ^a,b   Mellis, Scott J ^a,b   Gromada, Jesper ^b   Baras, Aris ^a   more..

^a AB)   (United States)

^b REGENERON PHARMACEUTICALS INC   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

^e GEISINGER HEALTH SYSTEM   (United States)

^f Division of Endocrinology and Metabolism   (Taiwan)

^g Cardiovascular Center   (Taiwan)

^h NATIONAL CHUNG HSING UNIVERSITY   (Taiwan)

ⁱ CHUNG SHAN MEDICAL UNIVERSITY   (Taiwan)

^j CHINA MEDICAL UNIVERSITY   (Taiwan)

^k NATIONAL YANG MING UNIVERSITY   (Taiwan)

^l NATIONAL DEFENSE MEDICAL CENTER   (Taiwan)

^m HARBOR UCLA MEDICAL CENTER   (United States)

ⁿ DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^o University of Copenhagen   (Denmark)

^p Herlev and Gentofte Hospital ^*  (Denmark)

^q GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^r FREDERIKSBERG HOSPITAL   (Denmark)

^s TNO   (Netherlands)

more..

Author keywords

[No Author keywords available]

Indexed keywords

EVINACUMAB; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; TRIACYLGLYCEROL; ANGIOPOIETIN; ANGPTL3 PROTEIN, HUMAN; ANGPTL3 PROTEIN, MOUSE; LIPID; MONOCLONAL ANTIBODY;

ADULT; ANGPTL3 GENE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CASE CONTROL STUDY; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; CORONARY ARTERY DISEASE; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE INCREASE; DRUG EFFECT; DYSLIPIDEMIA; EXON; FEMALE; FOLLOW UP; GENE; GENE INACTIVATION; GENE SEQUENCE; GENETIC VARIABILITY; HETEROZYGOTE; HUMAN; LOSS OF FUNCTION MUTATION; MAJOR CLINICAL STUDY; MALE; MOUSE; NONHUMAN; PHARMACOLOGICAL BLOCKING; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; TISSUE NECROSIS; TRIACYLGLYCEROL BLOOD LEVEL; VOLUNTEER; AGED; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; CARDIOVASCULAR DISEASES; CLINICAL TRIAL; DISEASE MODEL; DRUG EFFECTS; DYSLIPIDEMIAS; GENETICS; INBRED MOUSE STRAIN; LIPID METABOLISM; METABOLISM; MIDDLE AGED; MUTATION;

AGED; ANGIOPOIETINS; ANIMALS; ANTIBODIES, MONOCLONAL; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASES; CORONARY ARTERY DISEASE; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DYSLIPIDEMIAS; FEMALE; HUMANS; LIPID METABOLISM; LIPIDS; MALE; MICE; MICE, INBRED STRAINS; MIDDLE AGED; MUTATION;

EID: 85025435730     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1612790     Document Type: Article

References (38)

1. Romeo S, Pennacchio LA, Fu Y, et al. Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL. Nat Genet 2007; 39: 513-6.
2. Romeo S, Yin W, Kozlitina J, et al. Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans. J Clin Invest 2009; 119: 70-9.
3. Folsom AR, Peacock JM, Demerath E, Boerwinkle E. Variation in ANGPTL4 and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Metabolism 2008; 57: 1591-6.
4. Wang H, Eckel RH. Lipoprotein lipase: from gene to obesity. Am J Physiol Endocrinol Metab 2009; 297: E271-E288.
5. Dewey FE, Gusarova V, O'Dushlaine C, et al. Inactivating variants in ANGPTL4 and risk of coronary artery disease. N Engl J Med 2016; 374: 1123-33.
6. Jensen MK, Rimm EB, Rader D, et al. S447X variant of the lipoprotein lipase gene, lipids, and risk of coronary heart disease in 3 prospective cohort studies. Am Heart J 2009; 157: 384-90.
7. Sagoo GS, Tatt I, Salanti G, et al. Seven lipoprotein lipase gene polymorphisms, lipid fractions, and coronary disease: a HuGE association review and meta-analysis. Am J Epidemiol 2008; 168: 1233-46.
8. Khera AV, Won HH, Peloso GM, et al. Association of rare and common variation in the lipoprotein lipase gene with coronary artery disease. JAMA 2017; 317: 937-46.
9. Kersten S. Physiological regulation of lipoprotein lipase. Biochim Biophys Acta 2014; 1841: 919-33.
10. Wang Y, McNutt MC, Banfi S, et al. Hepatic ANGPTL3 regulates adipose tissue energy homeostasis. Proc Natl Acad Sci U S A 2015; 112: 11630-5.
11. Tikka A, Jauhiainen M. The role of ANGPTL3 in controlling lipoprotein metabolism. Endocrine 2016; 52: 187-93.
12. Liu J, Afroza H, Rader DJ, Jin W. Angiopoietin-like protein 3 inhibits lipoprotein lipase activity through enhancing its cleavage by proprotein convertases. J Biol Chem 2010; 285: 27561-70.
13. Shimamura M, Matsuda M, Yasumo H, et al. Angiopoietin-like protein3 regulates plasma HDL cholesterol through suppression of endothelial lipase. Arterioscler Thromb Vasc Biol 2007; 27: 366-72.
14. Minicocci I, Montali A, Robciuc MR, et al. Mutations in the ANGPTL3 gene and familial combined hypolipidemia: a clinical and biochemical characterization. J Clin Endocrinol Metab 2012; 97: E1266-E1275.
15. Pisciotta L, Favari E, Magnolo L, et al. Characterization of three kindreds with familial combined hypolipidemia caused by loss-of-function mutations of ANGPTL3. Circ Cardiovasc Genet 2012; 5: 42-50.
16. Musunuru K, Pirruccello JP, Do R, et al. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N Engl J Med 2010; 363: 2220-7.
17. Noto D, Cefalù AB, Valenti V, et al. Prevalence of ANGPTL3 and APOB gene mutations in subjects with combined hypolipidemia. Arterioscler Thromb Vasc Biol 2012; 32: 805-9.
18. Martín-Campos JM, Roig R, Mayoral C, et al. Identification of a novel mutation in the ANGPTL3 gene in two families diagnosed of familial hypobetalipoproteinemia without APOB mutation. Clin Chim Acta 2012; 413: 552-5.
19. Helgadottir A, Gretarsdottir S, Thorleifsson G, et al. Variants with large effects on blood lipids and the role of cholesterol and triglycerides in coronary disease. Nat Genet 2016; 48: 634-9.
20. Ando Y, Shimizugawa T, Takeshita S, et al. A decreased expression of angiopoietin-like 3 is protective against atherosclerosis in apoE-deficient mice. J Lipid Res 2003; 44: 1216-23.
21. Carey DJ, Fetterolf SN, Davis FD, et al. The Geisinger MyCode community health initiative: an electronic health recordlinked biobank for precision medicine research. Genet Med 2016; 18: 906-13.
22. Jørgensen AB, Frikke-Schmidt R, West AS, Grande P, Nordestgaard BG, Tybjærg-Hansen A. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J 2013; 34: 1826-33.
23. Varbo A, Benn M, Tybjærg-Hansen A, Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013; 61: 427-36.
24. Kraus WE, Granger CB, Sketch MH Jr, et al. A guide for a cardiovascular genomics biorepository: the CATHGEN experience. J Cardiovasc Transl Res 2015; 8: 449-57.
25. Kuo JZ, Sheu WH, Assimes TL, et al. Trans-ethnic fine mapping identifies a novel independent locus at the 3′ end of CDKAL1 and novel variants of several susceptibility loci for type 2 diabetes in a Han Chinese population. Diabetologia 2013; 56: 2619-28.
26. Assimes TL, Lee IT, Juang JM, et al. Genetics of coronary artery disease in Taiwan: a CardioMetaboChip Study by the Taichi Consortium. PLoS One 2016; 11(3): e0138014.
27. van Vlijmen BJ, van den Maagdenberg AM, Gijbels MJ, et al. Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. J Clin Invest 1994; 93: 1403-10.
28. Macdonald LE, Karow M, Stevens S, et al. Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes. Proc Natl Acad Sci U S A 2014; 111: 5147-52.
29. Murphy AJ, Macdonald LE, Stevens S, et al. Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice. Proc Natl Acad Sci U S A 2014; 111: 5153-8.
30. Gusarova V, Alexa CA, Wang Y, et al. ANGPTL3 blockade with a human monoclonal antibody reduces plasma lipids in dyslipidemic mice and monkeys. J Lipid Res 2015; 56: 1308-17.
31. van Vlijmen BJ, van 't Hof HB, Mol MJ, et al. Modulation of very low density lipoprotein production and clearance contributes to age- and gender-dependent hyperlipoproteinemia in apolipoprotein E3-Leiden transgenic mice. J Clin Invest 1996; 97: 1184-92.
32. Heinze G, Schemper M. A solution to the problem of separation in logistic regression. Stat Med 2002; 21: 2409-19.
33. Yang J, Lee SH, Goddard ME, Visscher PM. GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet 2011; 88: 76-82.
34. Kühnast S, van der Hoorn JW, Pieterman EJ, et al. Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin. J Lipid Res 2014; 55: 2103-12.
35. Wang Y, Gusarova V, Banfi S, Gromada J, Cohen JC, Hobbs HH. Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion. J Lipid Res 2015; 56: 1296-307.
36. Voight BF, Peloso GM, Orho-Melander M, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 2012; 380: 572-80.
37. Minicocci I, Santini S, Cantisani V, et al. Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis. J Lipid Res 2013; 54: 3481-90.
38. Stitziel NO, Khera AV, Wang X, et al. ANGPTL3 deficiency and protection against coronary artery disease. J Am Coll Cardiol 2017; 69: 2054-63.