Loss-of-function mutations in APOC3 and risk of ischemic vascular disease

New England Journal of Medicine

Volumn 371, Issue 1, 2014, Pages 32-41

  Jrøgensen, Anders Berg ^a,b   Frikke Schmidt, Ruth ^a,b,d   Nordestgaard, Børge G ^a,c,d,e   Tybjræg Hansen, Anne ^a,b,d,e  

^a Mental Health Services CPH   (Denmark)

^b Rigshospitalet   (Denmark)

^c Department of Clinical Biochemistry ^*  (Denmark)

^d Copenhagen General Population Study ^*  (Denmark)

^e GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN C3; TRIACYLGLYCEROL;

ADULT; AGED; APOC3 GENE; ARTICLE; DISEASE ASSOCIATION; DISEASE COURSE; EXON; FEMALE; FOLLOW UP; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; GENOTYPE; HETEROZYGOTE; HUMAN; INTRON; ISCHEMIC HEART DISEASE; ISCHEMIC VASCULAR DISEASE; LOSS OF FUNCTION MUTATION; MAJOR CLINICAL STUDY; MALE; NUCLEOTIDE SEQUENCE; POPULATION RESEARCH; PRIORITY JOURNAL; RISK ASSESSMENT; RISK REDUCTION; TRIACYLGLYCEROL BLOOD LEVEL; VASCULAR DISEASE;

ADULT; AGED; APOLIPOPROTEIN C-III; CHOLESTEROL, LDL; EXOME; FEMALE; GENOTYPE; HUMANS; INCIDENCE; ISCHEMIA; LIVER; MALE; MIDDLE AGED; MUTATION; MYOCARDIAL ISCHEMIA; RISK FACTORS; SEQUENCE ANALYSIS, DNA; TRIGLYCERIDES;

EID: 84903743893     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1308027     Document Type: Article

References (39)

1. Chapman MJ, Ginsberg HN, Amarenco P, et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011;32:1345-61.
2. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 2007;298:299-308. (Pubitemid 47080484)
3. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 2007;298:309-16. (Pubitemid 47080485)
4. The Emerging Risk Factors Collaboration. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009;302:1993-2000.
5. Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, Nordestgaard BG. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA 2008;300:2142-52.
6. Varbo A, Nordestgaard BG, Tybjaerg-Hansen A, Schnohr P, Jensen GB, Benn M. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population. Ann Neurol 2011;69:628-34.
7. 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.
8. Varbo A, Benn M, Tybjærg-Hansen AL, 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.
9. Ginsberg HN, Le NA, Goldberg IJ, et al. Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI: evidence that apolipoprotein CIII inhibits catabolism of triglyceriderich lipoproteins by lipoprotein lipase in vivo. J Clin Invest 1986;78:1287-95. (Pubitemid 17181567)
10. Ooi EM, Barrett PH, Chan DC, Watts GF. Apolipoprotein C-III: understanding an emerging cardiovascular risk factor. Clin Sci (Lond) 2008;114:611-24. (Pubitemid 351589061)
11. Windler E, Havel RJ. Inhibitory effects of C apolipoproteins from rats and humans on the uptake of triglyceride-rich lipoproteins and their remnants by the perfused rat liver. J Lipid Res 1985;26:556-65. (Pubitemid 15073727)
12. Clavey V, Lestavel-Delattre S, Copin C, Bard JM, Fruchart JC. Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII, and E. Arterioscler Thromb Vasc Biol 1995;15:963-71.
13. Sehayek E, Eisenberg S. Mechanisms of inhibition by apolipoprotein C of apolipoprotein E-dependent cellular metabolism of human triglyceride-rich lipoproteins through the low density lipoprotein receptor pathway. J Biol Chem 1991;266:18259-67. (Pubitemid 21908074)
14. Pollin TI, Damcott CM, Shen H, et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science 2008;322:1702-5.
15. Langsted A, Freiberg JJ, Nordestgaard BG. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction. Circulation 2008;118:2047-56.
16. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
17. Kamstrup PR, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation 2008;117:176-84.
18. Clarke R, Shipley M, Lewington S, et al. Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. Am J Epidemiol 1999;150:341-53. (Pubitemid 29383482)
19. Graham MJ, Lee RG, Bell TA III, et al. Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans. Circ Res 2013;112:1479-90.
20. Qin W, Sundaram M, Wang Y, et al. Missense mutation in APOC3 within the C-terminal lipid binding domain of human ApoC-III results in impaired assembly and secretion of triacylglycerol-rich very low density lipoproteins: evidence that ApoC-III plays a major role in the formation of lipid precursors within the microsomal lumen. J Biol Chem 2011;286:27769-80.
21. Sundaram M, Zhong S, Bou Khalil M, et al. Expression of apolipoprotein C-III in McA-RH7777 cells enhances VLDL assembly and secretion under lipid-rich conditions. J Lipid Res 2010;51:150-61.
22. Sundaram M, Zhong S, Bou Khalil M, et al. Functional analysis of the missense APOC3 mutation Ala23Thr associated with human hypotriglyceridemia. J Lipid Res 2010;51:1524-34.
23. Shaikh M, Wootton R, Nordestgaard BG, et al. Quantitative studies of transfer in vivo of low density, Sf 12-60, and Sf 60-400 lipoproteins between plasma and arterial intima in humans. Arterioscler Thromb 1991;11:569-77.
24. Nordestgaard BG, Wootton R, Lewis B. Selective retention of VLDL, IDL, and LDL in the arterial intima of genetically hyperlipidemic rabbits in vivo: molecular size as a determinant of fractional loss from the intima-inner media. Arterioscler Thromb Vasc Biol 1995;15:534-42.
25. Liu H, Labeur C, Xu CF, et al. Characterization of the lipid-binding properties and lipoprotein lipase inhibition of a novel apolipoprotein C-III variant Ala23Thr. J Lipid Res 2000;41:1760-71.
26. Bochem AE, van Capelleveen JC, Dallinga-Thie GM, et al. Two novel mutations in apolipoprotein C3 underlie atheroprotective lipid profiles in families. Clin Genet 2014;85:433-40.
27. Faustino NA, Cooper TA. Pre-mRNA splicing and human disease. Genes Dev 2003;17:419-37. (Pubitemid 36258756)
28. Petersen KF, Dufour S, Hariri A, et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med 2010;362:1082-9.
29. Atzmon G, Rincon M, Schechter CB, et al. Lipoprotein genotype and conserved pathway for exceptional longevity in humans. PLoS Biol 2006;4(4):e113.
30. Kozlitina J, Boerwinkle E, Cohen JC, Hobbs HH. Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance. Hepatology 2011;53:467-74.
31. Novelli V, Viviani Anselmi C, Roncarati R, et al. Lack of replication of genetic associations with human longevity. Biogerontology 2008;9:85-92.
32. Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007;357:2109-22. (Pubitemid 350146106)
33. Frikke-Schmidt R, Nordestgaard BG, Stene MC, et al. Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease. JAMA 2008;299:2524-32. (Pubitemid 351787208)
34. Johannsen TH, Kamstrup PR, Andersen RV, et al. Hepatic lipase, genetically elevated high-density lipoprotein, and risk of ischemic cardiovascular disease. J Clin Endocrinol Metab 2009;94:1264-73.
35. The AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011;365:2255-67. [Erratum, N Engl J Med 2012;367:189.]
36. Schwartz GG, Olsson AG, Abt M, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med 2012;367:2089-99.
37. Haase CL, Tybjærg-Hansen A, Qayyum AA, Schou J, Nordestgaard BG, Frikke-Schmidt R. LCAT, HDL cholesterol and ischemic cardiovascular disease: a mendelian randomization study of HDL cholesterol in 54,500 individuals. J Clin Endocrinol Metab 2012;97(2):E248-E256.
38. 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. [Erratum, Lancet 2012;380:564.]
39. Yao Z, Wang Y. Apolipoprotein C-III and hepatic triglyceride-rich lipoprotein production. Curr Opin Lipidol 2012;23:206-12.