Pharmacogenetics of apolipoprotein E gene during lipid-lowering therapy: Lipid levels and prevention of coronary heart disease

Pharmacogenomics

Volumn 9, Issue 10, 2008, Pages 1475-1486

  Nieminen, Tuomo ^a   Kähönen, Mika ^b   Viiri, Leena E ^a,b   Grönroos, Paula ^b,c   Lehtimäki, Terho ^b  

^a UNIVERSITY OF TAMPERE MEDICAL SCHOOL   (Finland)

^b TAMPERE UNIVERSITY HOSPITAL   (Finland)

^c UNIVERSITY OF TURKU   (Finland)

Author keywords

Apolipoprotein E; Atherosclerosis; Cholesterol; Ezetimibe; HMG CoA reductase inhibitors; Lipids; Pharmacogenetics; Polymorphisms; SNP; Statins

Indexed keywords

ANTILIPEMIC AGENT; APOLIPOPROTEIN E; ATORVASTATIN; BEZAFIBRATE; BILE ACID SEQUESTRANT; COLESTYRAMINE; EZETIMIBE; FENOFIBRATE; FLUINDOSTATIN; GEMFIBROZIL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MEVINOLIN; PLACEBO; PRAVASTATIN; SIMVASTATIN;

ALLELE; ATHEROSCLEROSIS; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CREATINE KINASE BLOOD LEVEL; DISEASE CARRIER; DISEASE COURSE; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; GENE FREQUENCY; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HUMAN; HYPERLIPIDEMIA; ISCHEMIC HEART DISEASE; LIPID BLOOD LEVEL; MONOTHERAPY; MUSCLE NECROSIS; MYALGIA; MYOPATHY; PHARMACOGENETICS; REVIEW; RHABDOMYOLYSIS; SIDE EFFECT;

APOLIPOPROTEINS E; CHOLESTEROL, LDL; CORONARY DISEASE; HUMANS; PHARMACOGENETICS; POLYMORPHISM, GENETIC;

EID: 55449097874     PISSN: 14622416     EISSN: 17448042     Source Type: Journal    
DOI: 10.2217/14622416.9.10.1475     Document Type: Review

References (92)

1. Shore VG, Shore B: Heterogeneity of human plasma very low density lipoproteins. Separation of species differing in protein components. Biochemistry 12, 502-507 (1973).
2. Rall SC Jr, Weisgraber KH, Mahley RW: Human apolipoprotein E. The complete amino acid sequence. J. Biol. Chem. 257, 4171-4178 (1982).
3. Wetterau JR, Aggerbeck LP, Rall SC Jr, Weisgraber KH: Human apolipoprotein E3 in aqueous solution. I. Evidence for two structural domains. J. Biol. Chem. 263, 6240-6248 (1988).
4. Utermann G, Hees M, Steinmetz A: Polymorphism of apolipoprotein E and occurrence of dysbetalipoproteinaemia in man. Nature 269, 604-607 (1977).
5. Weisgraber KH, Innerarity TL, Mahley RW: Abnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site. J. Biol. Chem. 257, 2518-2521 (1982).
6. Boerwinkle E, Utermann G: Simultaneous effects of the apolipoprotein E polymorphism on apolipoprotein E, apolipoprotein B, and cholesterol metabolism. Am. J. Hum. Genet. 42, 104-112 (1988).
7. Gregg RE, Zech LA, Schaefer EJ, Stark D, Wilson D, Brewer HB Jr: Abnormal in vivo metabolism of apolipoprotein E4 in humans. J. Clin. Invest. 78, 815-821 (1986).
8. Kesäniemi YA, Ehnholm C, Miettinen TA: Intestinal cholesterol absorption efficiency in man is related to apoprotein E phenotype. J. Clin. Invest. 80, 578-581 (1987).
9. van den Elzen P, Garg S, Leon L et al.: Apolipoprotein-mediated pathways of lipid antigen presentation. Nature 437, 906-910 (2005).
10. Stöhr J, Schindler G, Rothe G, Schmitz G: Enhanced upregutation of the Fc γ receptor IIIa (CD 16a) during in vitro differentiation of ApoE4/4 monocytes. Arterioscler. Thromb. Vasc. Biol. 18, 1424-1432 (1998).
11. Smit M, de Knijff P, Rosseneu M et al.: Apolipoprotein E polymorphism in The Netherlands and its effect on plasma lipid and apolipoprotein levels. Hum. Genet. 80, 287-292 (1988).
12. Utermann G, Pruin N, Steinmetz A: Polymorphism of apolipoproLein E. III. Effect of a single polymorphic gene locus on plasma lipid levels in man. Clin. Genet. 15, 63-72 (1979).
13. Mooijaart SP, Berbee JE, van Heemst D et al.: ApoE plasma levels and risk of cardiovascular mortality in old age. PLoS Med. 3, E176 (2006).
14. Zannis VI, Just PW, Breslow JL: Human apolipoprotein E isoprotein subclasses are genetically determined. Am. J. Hum. Genet. 33, 11-24 (1981).
15. Schiele F, De Bacquer D, Vincent-Viry M et al.: Apolipoprotein E serum concentration and polymorphism in six European countries: the ApoEurope Project. Atherosclerosis 152, 475-488 (2000).
16. Vaisi-Raygani A, Kharrazi H, Rahimi Z, Pourmotabbed T: Frequencies of apolipoprotein E polymorphism in a healthy Kurdish population from - Kermanshah, Iran. Hum. Biol. 79, 579-587 (2007).
17. Lehtimäki T, Moilanen T, Viikari J et al.: Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study. J Lipid Res. 31, 487-495 (1990).
18. Artiga MJ, Bullido MJ, Frank A et al.: Risk for Alzheimer's disease correlates with transcriptional activity of the APOE gene. Hum. Mol. Genet. 7, 1887-1892 (1998).
19. Laws SM, Taddei K, Martins G et al.: The -491AA polymorphism in the APOE gene is associated with increased plasma apoE levels in Alzheimer's disease. Neuroreport 10, 879-882 (1999).
20. Shepherd J, Cobbe SM, Ford I et al.: Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N. Engl. J. Med. 333, 1301-1307 (1995).
21. Downs JR, Clearfield M, Weis S et al.: Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 279, 1615-1622 (1998).
22. Scandinavian Simvastatin Survival Study Writing Group: Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344, 1383-1389 (1994).
23. Sacks FM, Pfeffer MA, Moye LA et al.: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N. Engl. J. Med. 335, 1001-1009 (1996).
24. Baigent C, Keech A, Kearney PM et al.: Efficacy and safety of cholesterol-lowering treatment: prospective meta-anatysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366, 1267-1278 (2005).
25. Bays HE, Neff D, Tomassini JE, Tershakovec AM: Ezetimibe: cholesterol lowering and beyond. Expert Rev. Cardiovasc. Ther. 6, 447-470 (2008).
26. Kastelein JJ, Akdim F, Stroes ES et al.: Simvastatin with or without ezetimibe in familial hypercholesterolemia. N. Engl. J. Med. 358, 1431-1443 (2008).
27. Mahley RW: Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240, 622-630 (1988).
28. Ilveskoski E. Loimaala A, Mercuri MF et al.: Apolipoprotein E polymorphism and carotid artery intima-media thickness in a random sample of middle-aged men. Atherosclerosis 153, 147-153 (2000).
29. Lehtimäki T, Moilanen T, Nikkari T et al.: Regional differences in apolipoprotein E polymorphism in Finland. Ann. Med. 23, 61-66 (1991).
30. Lehtimäki T, Pirttilä T, Mehta PD, Wisniewski HM, Frey H, Nikkari T: Apolipoprotein E (apoE) polymorphism and its influence on ApoE concentrations in the cerebrospinal fluid in Finnish patients with Alzheimer's disease. Hum. Genet. 95, 39-42 (1995).
31. Grönroos P, Raitakari OT, Kähönen M et al.: Influence of apolipoprotein E polymorphism on serum lipid and lipoprotein changes: a 21-year follow-up study from childhood to adulthood. The Cardiovascular Risk in Young Firms Study Clin. Chem. Lab. Med. 45, 592-598 (2007).
32. Ylä-Herttuala S, Jaakkola O, Ehnholm C et al.: Characterization of two lipoproteins containing apolipoproteins B and E from lesion-free human aortic intima. J. Lipid Res. 29, 563-572 (1988).
33. Murase T, Oka T, Yamada N et al.: Immunohistochemical localization of apolipoprotein E in atherosclerotic lesions of the aorta and coronary arteries. Atherosclerosis 60, 1-6 (1986).
34. Werb Z, Chin JR, Takemura R et al.: The cell and molecular biology of apolipoprotein E synthesis by macrophages. Ciba Found. Symp. 118, 155-171 (1986).
35. Mazzone T, Reardon C: Expression of heterologous human apolipoprotein E by J774 macrophages enhances cholesterol efflux to HDL3. J. Lipid Res. 35, 1345-1353 (1994).
36. Cullen P, Cignarella A, Brennhausen B, Mohr S, Assmann G, von Eckardstein A: Phenotype-dependent differences in apolipoprotein E metabolism and in cholesterol homeostasis in human monocyte-derived macrophages. J. Clin. Invest. 101, 1670-1677 (1998).
37. Riddell DR, Graham A, Owen JS: Apolipoprotein E inhibits platelet aggregation through the L-arginine: nitric oxide pathway. Implications for vascular disease. J. Biol. Chem. 272, 89-95 (1997).
38. Sacre SM, Stannard AK, Owen JS: Apolipoprotein E (apoE) isoforms differentially induce nitric oxide production in endothelial cells. FEBS Lett. 540, 181-187 (2003).
39. Saarelainen S, Lehtimäki T, Nikkilä M, Solakivi T, Nieminen MM, Jaakkola O: Association between apolipoprotein E alleles and autoantibodies against oxidised low-density lipoprotein. Clin. Chem. Lab. Med. 38, 477-478 (2000).
40. Rontu R, Ojala P, Hervonen A et al.: Apolipoprotein E genotype is related to plasma levels of C-reactive protein and lipids and to longevity in nonagenarians. Clin. Endocrinol. (Oxf.) 64, 265-270 (2006).
41. Grönroos P, Raitakari OT, Kähönen M et al.: Association of high sensitive C-reactive protein with apolipoprotein E polymorphism in children and young adults: the Cardiovascular Risk in Young Finns Study. Clin. Chem. Lab. Med. 46, 179-186 (2008).
42. Song Y, Stampfer MJ, Liu S: Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann. Intern. Med. 141, 137-147 (2004).
43. Bennet AM, di Angelantonio E, Ye Z et al.: Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA 298, 1300-1311 (2007).
44. Lambert JC, Brousseau T, Defosse V et al.: Independent association of an APOE gene promoter polymorphism with increased risk of myocardial infarction and decreased APOE plasma concentrations - the ECTIM study. Hum. Mol. Genet. 9, 57-61 (2000).
45. Shu YL, Dunleavey L, Bannister W et al.: Independent effects of the -219 G> T and ε 2/ε 3/ε 4 polymorphisms in the apolipoprotein E gene on coronary artery disease: the Southampton Atherosclerosis Study. Eur. J. Hum. Genet. 11, 437-443 (2003).
46. Kharrazi H, Vaisi-Raygani A, Sabokroh AR, Pourmotabbed T: Association between apolipoprotein E polymorphism and coronary artery disease in the Kermanshah population in Iran. Clin. Biochem. 39, 613-616 (2006).
47. Vaisi-Raygani A, Rahimi Z, Nomani H, Tavilani H, Pourmotabbed T: The presence of apolipoprotein ε4 and ε2 alleles augments the risk of coronary artery disease in Type 2 diabetic patients. Clin. Bioechem. 40, 1150-1156 (2007).
48. Abboud S, Viiri LE, Lutjohann D et al.: Associations of apolipoprotein E gene with ischemic stroke and intracranial atherosclerosis. Eur. J Hum. Genet. 16, 955-960 (2008).
49. Ilveskoski E, Perola M, Lehtimäki T et al.: Age-dependent association of apolipoprotein E genotype with coronary and aortic atherosclerosis in middle-aged men: an autopsy study. Circulation 100, 608-613 (1999).
50. Marenberg ME, Risch N, Berkman LF, Floderus B, de Faire U: Genetic susceptibility to death from coronary heart disease in a study of twins. N. Engl. J. Med. 330, 1041-1046 (1994).
51. O'Neill FH, Patel DD, Knight BL et al.: Determinants of variable response to statin treatment in patients with refractory familial hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 21, 832-837 (2001).
52. Ojala JP, Helve E, Ehnholm C, Aalto-Setala K, Kontula KK, Tikkanen MJ: Effect of apolipoprotein E polymorphism and XbaI polymorphism of apolipoprotein B on response to lovastatin treatment in familial and non-familial hypercholesterolaemia. J. Intern. Med. 230, 397-405 (1991).
53. Carmena R, Roederer G, Mailloux H, Lussier-Cacan S, Davignon J: The response to lovastatin treatment in patients with heterozygous familial hypercholesterolemia is modulated by apolipoprotein E polymorphism. Metabolism 42, 895-901 (1993).
54. Ballantyne CM, Herd JA, Stein EA et al.: Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy. J. Am. Coll. Cardiol. 36, 1572-1578 (2000).
55. Takane H, Miyata M, Burioka N et al.: Pharmacogenetic determinants of variability in lipid-lowering response to pravastatin therapy. J. Hum. Genet. 51, 822-826 (2006).
56. Kobayashi T, Homma Y: Effects of low-dose pravastatin on plasma levels of lipids and apolipoproteins in Japanese type II hyperlipoproteinemic subjects with apolipoprotein E phenotype E3/2, E3/3, and E4/3. J. Clin. Pharmacol. 41, 1055-1058 (2001).
57. Marques-Vidal P, Bongard V, Ruidavets JB, Fauvel J, Perret B, Ferrieres J: Effect of apolipoprotein E alleles and angiotensin-converting enzyme insertion/deletion polymorphisms on lipid and lipoprotein markers in middle-aged men and in patients with stable angina pectoris or healed myocardial infarction. Am. J. Cardiol. 92. 1102-1105 (2003).
58. Thompson JF, Man M, Johnson KJ et al.: An association study of 43 SNPs in 16 candidate genes with atorvastatin response. Pharmacogenomics J. 5, 352-358 (2005).
59. Ordovas JM, Lopez-Miranda.J, Perez-Jimenez F et al.: Effect of apolipoprotein E and A-IV phenotypes on the low density lipoprotein response to HMG CoA reductase inhibitor therapy. Atherosclerosis 113, 157-166 (1995).
60. Nestel F, Simons L, Barter P et al.: A comparative study of the efficacy of simvastatin and gemfibrozil in combined hyperlipoproteinemia: prediction of response by baseline lipids, apo E genotype, lipoprotein(a) and insulin. Atherosclerosis 129, 231-239 (1997).
61. Maitland-van der Zee AH, Jukema JW, Zwinderman AH et al.: Apolipoprotein-E polymorphismi and response to pravastatin in men with coronary artery disease (REGRESS). Acta Cardiol. 61, 327-331 (2006).
62. Donnelly LA, Palmer CN, Whitley AL et al.: Apolipoprotein E genotypes are associated with lipid-lowering responses to statin treatment in diabetes: a Go-DARTS study. Pharmacogenet. Genomics 18, 279-287 (2008).
63. Tavintharan S, Lim SC, Chan YH, Sum CF: Apolipoprotein E genotype affects the response to lipid-lowering therapy in Chinese patients with Type 2 diabetes mellitus. Diabetes Obes. Metab. 9, 81-86 (2607).
64. Pedro-Botet J, Schaefer EJ, Bakker-Arkema RG et al.: Apolipoprotein E genotype affects plasma lipid response to atorvastatin in a gender specific manner. Atherosclerosis 158, 183-193 (2001).
65. Maitland-van der Zee AH, Stricker BH, Klungel OH et al.: Adherence to and dosing of β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitors in the general population differs according to apolipoprotein E-genotypes. Pharmacogenetics 13, 219-223 (2003).
66. Berglund L, Wiklund O, Eggertsen G et al.: Apolipoprotein E phenotypes in familial hypercholesterolaemia: importance for expression of disease and response to therapy. J. Intern. Med. 233, 173-178 (1993).
67. O'Malley JP, Illingworth DR: The influence of apolipoprotein E phenotype on the response to lovastatin therapy in patients with heterozygous familial hypercholesterolemia. Metabolism 39, 150-154 (1990).
68. Christidis DS, Liberopoulos EN, Kakafika AI et al.: The effect of apolipoprotein E polymorphism on the response to lipid-lowering treatment with atorvastatin or fenofibrate. J. Cardiovasc. Pharmacol. Ther. 11, 211-221 (2006).
69. de Knijff P, Stalenhoef AF, Mol MJ et al.: Influence of apo E polymorphism on the response to simvastatin treatment in patients with heterozygous familial hypercholesterolemia. Atherosclerosis 83, 89-97 (1990).
70. Watanabe J, Kobayashi K, Umeda F et al.: Apolipoprotein E polymorphism affects the response to pravastatin on plasma apolipoproteins in diabetic patients. Diabetes Res. Clin. Pract. 20, 21-27 (1993).
71. Pena R, Lahoz C, Mostaza JM et al.: Effect of apoE genotype on the hypolipidaemic response to pravastatin in an outpatient setting. J. Intern. Med. 251, 518-525 (2002).
72. Garcia-Otin AL, Civeira F, Aristegui R et al.: Allelic polymorphism -491A/T in apo E gene modulates the lipid-lowering response in combined hyperlipidemia treatment. Eur J. Clin. Invest. 32, 421-428 (2002).
73. Mark L, Dani G, Fazekas O, Szule O, Kovacs H, Katona A: Effects of ezetimibe on lipids and lipoproteins in patients with hypercholesterolemia and different apolipoprotein E genotypes. Curr. Med. Res. Opin. 23, 1541-1548 (2007).
74. Gerdes LU, Gerdes C, Kervinen K et al.: The apolipoprotein ε4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction: a substudy of the Scandinavian Simvastatin Survival Study. Circulation 101, 1366-1371 (2000).
75. Maitland-van der Zee AH, Stricker BH, Klungel OH et al.: The effectiveness of hydroxy-methylglutaryl coenzyme A reductase inhibitors (statins) in the elderly is not influenced by apolipoprotein E genotype. Pharmacogenetics 12, 647-653 (2002).
76. Chiodini BD, Franzosi MG, Barlera S et al.: Apolipoprotein E polymorphisms influence effect of pravastatin on survival after myocardial infarction in a Mediterranean population: the GISSI-Prevenzione study. Eur. heart J. 28, 1977-1983 (2007).
77. Ilveskoski E, Lehtimäki T, Laaksonen R et al.: Improvement of myocardial blood flow by lipid-lowering therapy with pravastatin is modulated by apolipoprotein E genotype. Scand. J. Clin. Lab. Invest. 67, 723-734 (2007).
78. Kajinami K, Akao H, Polisecki E, Schaefer EJ: Pharmacogenomics of statin responsiveness. Am. J. Cardiol. 96, K65-K70; discussion K34-K35 (2005).
79. Schmitz G, Schmitz-Madry A, Ugocsai P: Pharmacogenetics and pharmacogenomics of cholesterol-lowering therapy. Curr. Opin. Lipidol. 18, 164-173 (2007).
80. Mangravite LM, Krauss RM: Pharmacogenomics of statin response. Curr. Opin. Lipidol. 18, 409-414 (2007).
81. Mangravite LM, Thorn CF, Krauss RM: Clinical implications of pharmacogenomics of statin treatment. Pharmacogenomics J. 6, 360-374 (2006).
82. Harper CR, Jacobson TA: The broad spectrum of statin myopathy: from myalgia to rhabdomyolysis. Curr. Opin. Lipidol. 18, 401-408 (2007).
83. Laaksonen R, Katajamaa M, Paiva H et al.: A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statininduced changes in muscle. PLoS ONE 1, E97 (2006).
84. Sanllehy C, Casals E, Rodriguez-Villar C et al.: Lack of interaction of apolipoprotein E phenotype with the lipoprotein response to lovastatin or gemnfibrozil in patients with primary hypercholesterolemia. Metabolism 47, 560-565 (1998).
85. Vohl MC, Szots F, Lelievre M et al.: Influence of LDL receptor gene mutation and apo E polymorphism on lipoprotein response to simvastatin treatment among adolescents with heterozygous familial hypercholesterolemia. Atherosclerosis 160, 361-368 (2002).
86. Ye P, Shang Y, Ding X: The influence of apolipoprotein B and E gene polymorphisms on the response to simvastatin therapy in patients with hyperlipidemia. Chin. Med. Sci. J. 18, 9-13 (2003).
87. Vega GL, Weiner M, Kolsch H et al.: The effects of gender and CYP46 and apo E polymorphism on 24S-hydroxycholesterol levels in Alzheimer's patients treated with statins. Curr. Alzbeimer Res. 1, 71-77 (2004).
88. Fiegenbaum M, da Silveira FR, van der Sand CR et al.: Pharmacogenetic study of apolipoprotein E, cholesteryl ester transfer protein and hepatic lipase genes and simvastatin therapy in Brazilian subjects. Clin. Chim. Acta 362, 182-188 (2005).
89. Miltiadous G, Xenophontos S, Bairaktari E, Ganotakis M, Cariolou M, Elisaf M: Genetic and environmental factors affecting the response to statin therapy in patients with molecularly defined familial hypercholesterolaemia. Pharmacogenet. Genomics 15, 219-225 (2005).
90. Zuccam P, Mombelli G, Calabresi L, Baldassame D, Palmi I, Sirtori CR: Tolerability of statins is not linked to CYP450 polymorphisms, but reduced CYP2D6 metabolism improves cholesteraemic response to simvastatin and fluvastatin. Pharmacol. Res. 55, 310-317 (2007).
91. Chou CY, Lin YL, Huang YC et al.: Structural variation in human apolipoprotein E3 and E4: secondary structure, tertiary structure, and size distribution. Biophys. J. 88, 455-466 (2005).
92. Laws SM, Hone E, Gandy S, Martins RN: Expanding the association between the APOE gene and the risk of Alzheimer's disease: possible roles for APOE promoter polymorphisms and alterations in APOE transcription. J. Neurochem. 84, 1215-1236 (2003).