The Genetics of High-Density Lipoprotein Metabolism: Clinical Relevance for Therapeutic Approaches

American Journal of Cardiology

Volumn 104, Issue 10 SUPPL., 2009, Pages 22E-31E

  Strang, Aart C ^a   Hovingh, G Kees ^a   Stroes, Erik S G ^a   Kastelein, John J P ^a  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

2 METHYLPROPANETHIOIC ACID S [2 [1 (2 ETHYLBUTYL)CYCLOHEXYLCARBOXAMIDO]PHENYL] ESTER; ABC TRANSPORTER A1; ADENOSINE TRIPHOSPHATE; ANACETRAPIB; APOLIPOPROTEIN A1; CHOLESTEROL ESTER TRANSFER PROTEIN; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; D 4F PEPTIDE; DALCETRAPIB; ETC 216; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; PEPTIDE; PHOSPHATIDYLCHOLINE STEROL ACYLTRANSFERASE; PHOSPHOLIPID TRANSFER PROTEIN; RVX 208; TORCETRAPIB; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG;

ANGIOCARDIOGRAPHY; ARTICLE; ATHEROSCLEROSIS; BLOOD PRESSURE; CALCIUM CELL LEVEL; CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; CORONARY ARTERY ATHEROSCLEROSIS; CORONARY ARTERY DISEASE; CORONARY RISK; DISEASE MARKER; DRUG TOLERABILITY; DRUG WITHDRAWAL; FAMILY STUDY; GENE CASSETTE; GENE DELETION; GENE IDENTIFICATION; GENE INSERTION; GENE LOCUS; GENE MUTATION; GENETIC DISORDER; GENETIC VARIABILITY; HETEROZYGOSITY; HUMAN; HYPOALPHALIPOPROTEINEMIA; INTRAVASCULAR ULTRASOUND; LIPOPROTEIN BLOOD LEVEL; LIPOPROTEIN METABOLISM; METABOLIC DISORDER; MISSENSE MUTATION; NONHUMAN; NONSENSE MUTATION; PHENOTYPE; POPULATION RESEARCH; PRIORITY JOURNAL; SIDE EFFECT; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTOLIC BLOOD PRESSURE; VASCULAR DISEASE;

EID: 71749083863     PISSN: 00029149     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.amjcard.2009.09.016     Document Type: Article

References (82)

1. Lewis S.J. Prevention and treatment of atherosclerosis: a practitioner's guide for 2008. Am J Med 122 (2009) S38-S50
2. Gotto Jr. A.M., and Brinton E.A. Assessing low levels of high-density lipoprotein cholesterol as a risk factor in coronary heart disease: a working group report and update. J Am Coll Cardiol 43 (2004) 717-724
3. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285 (2001) 2486-2497
4. Gordon D.J., and Rifkind B.M. High-density lipoprotein-the clinical implications of recent studies. N Engl J Med 321 (1989) 1311-1316
5. Chapman M.J., Assmann G., Fruchart J.C., Shepherd J., and Sirtori C. Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid-a position paper developed by the European Consensus Panel on HDL-C. Curr Med Res Opin 20 (2004) 1253-1268
6. Holleboom A.G., Vergeer M., Hovingh G.K., Kastelein J.J., and Kuivenhoven J.A. The value of HDL genetics. Curr Opin Lipidol 19 (2008) 385-394
7. Huuskonen J., Olkkonen V.M., Jauhiainen M., and Ehnholm C. The impact of phospholipid transfer protein (PLTP) on HDL metabolism. Atherosclerosis 155 (2001) 269-281
8. Kontush A., and Chapman M.J. Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol Rev 58 (2006) 342-374
9. Hovingh G.K., de Groot E., van der Steeg W., Boekholdt S.M., Hutten B.A., Kuivenhoven J.A., and Kastelein J.J. Inherited disorders of HDL metabolism and atherosclerosis. Curr Opin Lipidol 16 (2005) 139-145
10. Klos K.L., and Kullo I.J. Genetic determinants of HDL: monogenic disorders and contributions to variation. Curr Opin Cardiol 22 (2007) 344-351
11. Favari E., Gomaraschi M., Zanotti I., Bernini F., Lee-Rueckert M., Kovanen P.T., Sirtori C.R., Franceschini G., and Calabresi L. A unique protease-sensitive high density lipoprotein particle containing the apolipoprotein A-I(Milano) dimer effectively promotes ATP-binding cassette A1-mediated cell cholesterol efflux. J Biol Chem 282 (2007) 5125-5132
12. Bielicki J.K., and Oda M.N. Apolipoprotein A-I(Milano) and apolipoprotein A-I(Paris) exhibit an antioxidant activity distinct from that of wild-type apolipoprotein A-I. Biochemistry 41 (2002) 2089-2096
13. Gualandri V., Franceschini G., Sirtori C.R., Gianfranceschi G., Orsini G.B., Cerrone A., and Menotti A. AIMilano apoprotein identification of the complete kindred and evidence of a dominant genetic transmission. Am J Hum Genet 37 (1985) 1083-1097
14. Sirtori C.R., Calabresi L., Franceschini G., Baldassarre D., Amato M., Johansson J., Salvetti M., Monteduro C., Zulli R., Muiesan M.L., and Agabiti-Rosei E. Cardiovascular status of carriers of the apolipoprotein A-I(Milano) mutant: the Limone sul Garda study. Circulation 103 (2001) 1949-1954
15. Hovingh G.K., Brownlie A., Bisoendial R.J., Dube M.P., Levels J.H., Petersen W., Dullaart R.P., Stroes E.S., Zwinderman A.H., de Groot E., et al. A novel apoA-I mutation (L178P) leads to endothelial dysfunction, increased arterial wall thickness, and premature coronary artery disease. J Am Coll Cardiol 44 (2004) 1429-1435
16. Miller M., Aiello D., Pritchard H., Friel G., and Zeller K. Apolipoprotein A-I(Zavalla) (Leu159->Pro): HDL cholesterol deficiency in a kindred associated with premature coronary artery disease. Arterioscler Thromb Vasc Biol 18 (1998) 1242-1247
17. Moriyama K., Sasaki J., Takada Y., Matsunaga A., Fukui J., Albers J.J., and Arakawa K. A cysteine-containing truncated apo A-I variant associated with HDL deficiency. Arterioscler Thromb Vasc Biol 16 (1996) 1416-1423
18. Recalde D., Velez-Carrasco W., Civeira F., Cenarro A., Gomez-Coronado D., Ordovas J.M., and Pocovi M. Enhanced fractional catabolic rate of apo A-I and apo A-II in heterozygous subjects for apo A-I(Zaragoza) (L144R). Atherosclerosis 154 (2001) 613-623
19. Krimbou L., Jahagirdar R., Bailey D., Hafiane A., Ruel I., Wong N., Wagner G.S., Chiacchia F., Gordon A., Hansen H.C., Johansson J., and Genest J. Compound RVX-208 modulates HDL-C levels and function in non-human primates and in early (phase I) human trials. Circulation 118 (2008) S_371 Abstract 1696
20. Chiesa G., Parolini C., and Sirtori C.R. Acute effects of high-density lipoproteins: biochemical basis and clinical findings. Curr Opin Cardiol 23 (2008) 379-385
21. Eriksson M., Carlson L.A., Miettinen T.A., and Angelin B. Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I: potential reverse cholesterol transport in humans. Circulation 100 (1999) 594-598
22. Nanjee M.N., Cooke C.J., Garvin R., Semeria F., Lewis G., Olszewski W.L., and Miller N.E. Intravenous apoA-I/lecithin discs increase pre-β-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans. J Lipid Res 42 (2001) 1586-1593
23. Nissen S.E., Tsunoda T., Tuzcu E.M., Schoenhagen P., Cooper C.J., Yasin M., Eaton G.M., Lauer M.A., Sheldon W.S., Grines C.L., et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 290 (2003) 2292-2300
24. Tardif J.C., Gregoire J., L'Allier P.L., Ibrahim R., Lesperance J., Heinonen T.M., Kouz S., Berry C., Basser R., Lavoie M.A., Guertin M.C., and Rodes-Cabau J. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 297 (2007) 1675-1682
25. Navab M., Anantharamaiah G.M., Hama S., Garber D.W., Chaddha M., Hough G., Lallone R., and Fogelman A.M. Oral administration of an Apo A-I mimetic peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol. Circulation 105 (2002) 290-292
26. Van Lenten B.J., Wagner A.C., Anantharamaiah G.M., Navab M., Reddy S.T., Buga G.M., and Fogelman A.M. Apolipoprotein A-I mimetic peptides. Curr Atheroscler Rep 11 (2009) 52-57
27. Bloedon L.T., Dunbar R., Duffy D., Pinell-Salles P., Norris R., DeGroot B.J., Movva R., Navab M., Fogelman A.M., and Rader D.J. Safety, pharmacokinetics, and pharmacodynamics of oral apoA-I mimetic peptide D-4F in high-risk cardiovascular patients. J Lipid Res 49 (2008) 1344-1352
28. Jahagirdar R., Genest J., Hansen H.C., Nicholls C.D., Attwell S., McLure K.G., Wagner G.S., Johansson J., and Wong N.C. RVX-208: A small molecule that increases ApoA-I, HDL-C, and cholesterol efflux. Atheroscler Suppl 9 (2008) 2
29. Burgess J.W., Neville T.A., Rouillard P., Harder Z., Beanlands D.S., and Sparks D.L. Phosphatidylinositol increases HDL-C levels in humans. J Lipid Res 46 (2005) 350-355
30. Glomset J.A. The plasma lecithins: cholesterol acyltransferase reaction. J Lipid Res 9 (1968) 155-167
31. Brooks-Wilson A., Marcil M., Clee S.M., Zhang L.H., Roomp K., van Dam M., Yu L., Brewer C., Collins J.A., Molhuizen H.O., et al. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet 22 (1999) 336-345
32. Brunham L.R., Singaraja R.R., and Hayden M.R. Variations on a gene: rare and common variants in ABCA1 and their impact on HDL cholesterol levels and atherosclerosis. Annu Rev Nutr 26 (2006) 105-129
33. Hersberger M., and von E.A. Modulation of high-density lipoprotein cholesterol metabolism and reverse cholesterol transport. Handb Exp Pharmacol (2005) 537-561
34. Haghpassand M., Bourassa P.A., Francone O.L., and Aiello R.J. Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels. J Clin Invest 108 (2001) 1315-1320
35. van Dam M.J., de Groot E., Clee S.M., Hovingh G.K., Roelants R., Brooks-Wilson A., Zwinderman A.H., Smit A.J., Smelt A.H., Groen A.K., Hayden M.R., and Kastelein J.J. Association between increased arterial-wall thickness and impairment in ABCA1-driven cholesterol efflux: an observational study. Lancet 359 (2002) 37-42
36. Repa J.J., Turley S.D., Lobaccaro J.A., Medina J., Li L., Lustig K., Shan B., Heyman R.A., Dietschy J.M., and Mangelsdorf D.J. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 289 (2000) 1524-1529
37. Lu T.T., Repa J.J., and Mangelsdorf D.J. Orphan nuclear receptors as eLiXiRs and FiXeRs of sterol metabolism. J Biol Chem 276 (2001) 37735-37738
38. Miao B., Zondlo S., Gibbs S., Cromley D., Hosagrahara V.P., Kirchgessner T.G., Billheimer J., and Mukherjee R. Raising HDL cholesterol without inducing hepatic steatosis and hypertriglyceridemia by a selective LXR modulator. J Lipid Res 45 (2004) 1410-1417
39. Rader D.J. Liver X receptor and farnesoid X receptor as therapeutic targets. Am J Cardiol 100 suppl (2007) n15-n19
40. Barter P.J., Brewer Jr. H.B., Chapman M.J., Hennekens C.H., Rader D.J., and Tall A.R. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol 23 (2003) 160-167
41. Shah P.K. Inhibition of CETP as a novel therapeutic strategy for reducing the risk of atherosclerotic disease. Eur Heart J 28 (2007) 5-12
42. Koizumi J., Mabuchi H., Yoshimura A., Michishita I., Takeda M., Itoh H., Sakai Y., Sakai T., Ueda K., and Takeda R. Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia. Atherosclerosis 58 (1985) 175-186
43. Inazu A., Brown M.L., Hesler C.B., Agellon L.B., Koizumi J., Takata K., Maruhama Y., Mabuchi H., and Tall A.R. Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Engl J Med 323 (1990) 1234-1238
44. Inazu A., Jiang X.C., Haraki T., Yagi K., Kamon N., Koizumi J., Mabuchi H., Takeda R., Takata K., Moriyama Y., et al. Genetic cholesteryl ester transfer protein deficiency caused by two prevalent mutations as a major determinant of increased levels of high density lipoprotein cholesterol. J Clin Invest 94 (1994) 1872-1882
45. Sviridov D., and Nestel P.J. Genetic factors affecting HDL levels, structure, metabolism and function. Curr Opin Lipidol 18 (2007) 157-163
46. Zhong S., Sharp D.S., Grove J.S., Bruce C., Yano K., Curb J.D., and Tall A.R. Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels. J Clin Invest 97 (1996) 2917-2923
47. Curb J.D., Abbott R.D., Rodriguez B.L., Masaki K.H., Curb J.D., and Petrovitch H. A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly. J Lipid Res 45 (2004) 948-953
48. Moriyama Y., Okamura T., Inazu A., Doi M., Iso H., Mouri Y., Ishikawa Y., Suzuki H., Iida M., Koizumi J., Mabuchi H., and Komachi Y. A low prevalence of coronary heart disease among subjects with increased high-density lipoprotein cholesterol levels, including those with plasma cholesteryl ester transfer protein deficiency. Prev Med 27 (1998) 659-667
49. Boekholdt S.M., Sacks F.M., Jukema J.W., Shepherd J., Freeman D.J., McMahon A.D., Cambien F., Nicaud V., de Grooth G.J., Talmud P.J., et al. Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects. Circulation 111 (2005) 278-287
50. van Acker B.A., Botma G.J., Zwinderman A.H., Kuivenhoven J.A., Dallinga-Thie G.M., Sijbrands E.J., Boer J.M., Seidell J.C., Jukema J.W., Kastelein J.J., Jansen H., Verhoeven A.J., and REGRESS Study Group. High HDL cholesterol does not protect against coronary artery disease when associated with combined cholesteryl ester transfer protein and hepatic lipase gene variants. Atherosclerosis 200 (2008) 161-167
51. Bruce C., Sharp D.S., and Tall A.R. Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemia. J Lipid Res 39 (1998) 1071-1078
52. Thompson A., Di Angelantonio E., Sarwar N., Erqou S., Saleheen D., Dullaart R.P., Keavney B., Ye Z., and Danesh J. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA 299 (2008) 2777-2788
53. Davidson M.H., McKenney J.M., Shear C.L., and Revkin J.H. Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels. J Am Coll Cardiol 48 (2006) 1774-1781
54. Barter P.J., Caulfield M., Eriksson M., Grundy S.M., Kastelein J.J., Komajda M., Lopez-Sendon J., Mosca L., Tardif J.C., Waters D.D., et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 357 (2007) 2109-2122
55. Hu X., Dietz J.D., Xia C., Knight D.R., Loging W.T., Smith A.H., Yuan H., Perry D.A., and Keiser J. Torcetrapib induces aldosterone and cortisol production by an intracellular calcium-mediated mechanism independently of cholesteryl ester transfer protein inhibition. Endocrinology 150 (2009) 2211-2219
56. Forrest M.J., Bloomfield D., Briscoe R.J., Brown P.N., Cumiskey A.M., Ehrhart J., Hershey J.C., Keller W.J., Ma X., McPherson H.E., et al. Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. Br J Pharmacol 154 (2008) 1465-1473
57. de Grooth G.J., Kuivenhoven J.A., Stalenhoef A.F., de Graaf J., Zwinderman A.H., Posma J.L., van T.A., and Kastelein J.J. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation 105 (2002) 2159-2165
58. Stroes E.S., Kastelein J.J., Bernardeau A., Blum D., Clerc R.G., Campos L., and Niesor E. Absence of effect of R1658/JTT-705 on blood pressure and tissue expression of renin-angiotensin system related genes in rats [abstract]. J Am Coll Cardiol 51 suppl 1 (2008) A322
59. Bloomfield D., Carlson G.L., Sapre A., Tribble D., McKenney J.M., Littlejohn III T.W., Sisk C.M., Mitchel Y., and Pasternak R.C. Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients. Am Heart J 157 (2009) 352-360
60. Jaye M., Lynch K.J., Krawiec J., Marchadier D., Maugeais C., Doan K., South V., Amin D., Perrone M., and Rader D.J. A novel endothelial-derived lipase that modulates HDL metabolism. Nat Genet 21 (1999) 424-428
61. Paradis M.E., Badellino K.O., Rader D.J., Deshaies Y., Couture P., Archer W.R., Bergeron N., and Lamarche B. Endothelial lipase is associated with inflammation in humans. J Lipid Res 47 (2006) 2808-2813
62. Ishida T., Choi S., Kundu R.K., Hirata K., Rubin E.M., Cooper A.D., and Quertermous T. Endothelial lipase is a major determinant of HDL level. J Clin Invest 111 (2003) 347-355
63. Jensen M.K., Rimm E.B., Mukamal K.J., Edmondson A.C., Rader D.J., Vogel U., Tjønneland A., Sørensen T.I., Schmidt E.B., and Overvad K. The T111I variant in the endothelial lipase gene and risk of coronary heart disease in three independent populations. Eur Heart J 30 (2009) 1584-1589
64. Edmondson A.C., Brown R.J., Kathiresan S., Cupples L.A., Demissie S., Manning A.K., Jensen M.K., Rimm E.B., Wang J., Rodrigues A., et al. Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans. J Clin Invest 119 (2009) 1042-1050
65. Rye K.A., Hime N.J., and Barter P.J. Evidence that cholesteryl ester transfer protein-mediated reductions in reconstituted high density lipoprotein size involve particle fusion. J Biol Chem 272 (1997) 3953-3960
66. Schgoer W., Mueller T., Jauhiainen M., Wehinger A., Gander R., Tancevski I., Salzmann K., Eller P., Ritsch A., Haltmayer M., et al. Low phospholipid transfer protein (PLTP) is a risk factor for peripheral atherosclerosis. Atherosclerosis 196 (2008) 219-226
67. Schlitt A., Bickel C., Thumma P., Blankenberg S., Rupprecht H.J., Meyer J., and Jiang X.C. High plasma phospholipid transfer protein levels as a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol 23 (2003) 1857-1862
68. Schlitt A., Blankenberg S., Bickel C., Lackner K.J., Heine G.H., Buerke M., Werdan K., Maegdefessel L., Raaz U., Rupprecht H.J., Munzel T., and Jiang X.C. PLTP activity is a risk factor for subsequent cardiovascular events in CAD patients under statin therapy: the AtheroGene Study. J Lipid Res 50 (2009) 723-729
69. de Vries R., Dallinga-Thie G.M., Smit A.J., Wolffenbuttel B.H., van Tol A., and Dullaart R.P. Elevated plasma phospholipid transfer protein activity is a determinant of carotid intima-media thickness in type 2 diabetes mellitus. Diabetologia 49 (2006) 398-404
70. Engler M.B., Pullinger C.R., Malloy M.J., Natanzon Y., Kulkarni M.V., Song J., Eng C., Huuskonen J., Rivera C., Poon A., et al. Genetic variation in phospholipid transfer protein modulates lipoprotein profiles in hyperalphalipoproteinemia. Metabolism 57 (2008) 1719-1724
71. Kiss R.S., Kavaslar N., Okuhira K., Freeman M.W., Walter S., Milne R.W., McPherson R., and Marcel Y.L. Genetic etiology of isolated low HDL syndrome: incidence and heterogeneity of efflux defects. Arterioscler Thromb Vasc Biol 27 (2007) 1139-1145
72. Tu A.Y., and Albers J.J. DNA sequences responsible for reduced promoter activity of human phospholipid transfer protein by fibrate. Biochem Biophys Res Commun 264 (1999) 802-807
73. Kahri J., Sane T., van Tol A., and Taskinen M.R. Effect of gemfibrozil on the regulation of HDL subfractions in hypertriglyceridaemic patients. J Intern Med 238 (1995) 429-436
74. Jonas A. Lecithin cholesterol acyltransferase. Biochim Biophys Acta 1529 (2000) 245-256
75. Kuivenhoven J.A., Pritchard H., Hill J., Frohlich J., Assmann G., and Kastelein J. The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes. J Lipid Res 38 (1997) 191-205
76. Zhang K., Zhang S., Zheng K., Hou Y., Liao L., He Y., Zhang L., Nebert D.W., Shi J., Su Z., and Xiao C. Novel P143L polymorphism of the LCAT gene is associated with dyslipidemia in Chinese patients who have coronary atherosclerotic heart disease. Biochem Biophys Res Commun 318 (2004) 4-10
77. Krause BR. The Use Of LCAT Infusion To Treat Acute Coronary Syndromes. National Institutes of Health. 1-9-2008. 1-6-2009. Ref Type: Online Source.
78. Amar M.J., Shamburek R.D., Vaisman B., Knapper C.L., Foger B., Hoyt Jr. R.F., Santamarina-Fojo S., Brewer Jr. H.B., and Remaley A.T. Adenoviral expression of human lecithin-cholesterol acyltransferase in nonhuman primates leads to an antiatherogenic lipoprotein phenotype by increasing high-density lipoprotein and lowering low-density lipoprotein. Metabolism 58 (2009) 568-575
79. Cohen J.C., Boerwinkle E., Mosley Jr. T.H., and Hobbs H.H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354 (2006) 1264-1272
80. Kathiresan S., Melander O., Anevski D., Guiducci C., Burtt N.P., Roos C., Hirschhorn J.N., Berglund G., Hedblad B., Groop L., et al. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med 358 (2008) 1240-1249
81. Kathiresan S., Willer C.J., Peloso G.M., Demissie S., Musunuru K., Schadt E.E., Kaplan L., Bennett D., Li Y., Tanaka T., et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 41 (2009) 56-65
82. Willer C.J., Sanna S., Jackson A.U., Scuteri A., Bonnycastle L.L., Clarke R., Heath S.C., Timpson N.J., Najjar S.S., Stringham H.M., et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 40 (2008) 161-169