Pharmacogenetics of the antiplatelet effect of aspirin

Current Pharmaceutical Design

Volumn 18, Issue 33, 2012, Pages 5294-5308

  Würtz, Morten ^a   Kristensen, Steen Dalby ^a   Hvas, Anne Mette ^a   Grove, Erik Lerkevang ^a  

^a AARHUS UNIVERSITY HOSPITAL   (Denmark)

Author keywords

Aspirin; Genetic testing; Pharmacogenetics; Platelet aggregation inhibitors; Platelet function tests; Platelet glycoprotein IIb IIIa complex; Polymorphisms

Indexed keywords

1 ALKYL 2 ACETYLGLYCEROPHOSPHOCHOLINE ESTERASE; ACETYLSALICYLIC ACID; ALPHA2 INTEGRIN; BLOOD CLOTTING FACTOR 13; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; GLUCURONOSYLTRANSFERASE; GLYCOPROTEIN IB ALPHA; GLYCOPROTEIN IIB; GLYCOPROTEIN VI; PURINERGIC P2Y1 RECEPTOR; PURINERGIC P2Y12 RECEPTOR; THROMBOXANE A2 RECEPTOR;

ANTICOAGULATION; ARTICLE; BERNARD SOULIER DISEASE; CORONARY ARTERY BYPASS GRAFT; CORONARY ARTERY DISEASE; DRUG EFFECT; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; GENETIC POLYMORPHISM; GLANZMANN DISEASE; HEART INFARCTION; HEMOSTASIS; HUMAN; NONHUMAN; PERCUTANEOUS CORONARY INTERVENTION; PHARMACODYNAMICS; PHARMACOGENETICS; PRIORITY JOURNAL; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION;

ANIMALS; ASPIRIN; BLOOD PLATELETS; CYCLOOXYGENASE INHIBITORS; DRUG RESISTANCE; GENOTYPE; HEMORRHAGE; HUMANS; PHARMACOGENETICS; PHENOTYPE; PLATELET AGGREGATION INHIBITORS; PLATELET FUNCTION TESTS; PLATELET MEMBRANE GLYCOPROTEINS; POLYMORPHISM, GENETIC; PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES; PURINERGIC P2Y RECEPTOR ANTAGONISTS; RECEPTORS, PURINERGIC P2Y; RISK FACTORS; TREATMENT OUTCOME;

EID: 84870048259     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161212803251907     Document Type: Article

References (181)

1. Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007 Dec 13; 357(24): 2482-94.
2. Hankey GJ, Eikelboom JW. Aspirin resistance. Lancet 2006 Feb 18; 367(9510): 606-17.
3. Bray PF. Integrin polymorphisms as risk factors for thrombosis. Thromb Haemost 1999 Aug; 82(2): 337-44.
4. Hankey GJ, Eikelboom JW. Antiplatelet drugs. Med J Aust 2003 Jun 2; 178(11): 568-74.
5. Shattil SJ. Signaling through platelet integrin alpha IIb beta 3: inside-out, outside-in, and sideways. Thromb Haemost 1999 Aug; 82(2): 318-25.
6. Woronowicz K, Dilks JR, Rozenvayn N, et al. The platelet actin cytoskeleton associates with SNAREs and participates in alphagranule secretion. Biochemistry 2010 Jun 1; 49(21): 4533-42.
7. Flaumenhaft R, Dilks JR, Rozenvayn N, Monahan-Earley RA, Feng D, Dvorak AM. The actin cytoskeleton differentially regulates platelet alpha-granule and dense-granule secretion. Blood 2005 May 15; 105(10): 3879-87.
8. Italiano JE, Jr., Richardson JL, Patel-Hett S, et al. Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. Blood 2008 Feb 1; 111(3): 1227-33.
9. Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost 2011 May; 105 Suppl 1: S13-S33.
10. Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med 2008 Aug 28; 359(9): 938-49.
11. McNicol A, Israels SJ. Platelets and anti-platelet therapy. J Pharmacol Sci 2003 Dec; 93(4): 381-96.
12. Patrono C, Coller B, FitzGerald GA, Hirsh J, Roth G. Plateletactive drugs: the relationships among dose, effectiveness, and side effects: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004 Sep; 126(3 Suppl): 234S-64S.
13. Pedersen AK, Fitz Gerald GA. Dose-related kinetics of aspirin. Presystemic acetylation of platelet cyclooxygenase. N Engl J Med 1984 Nov 8; 311(19): 1206-11.
14. Patrono C, Garcia Rodriguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 2005 Dec 1; 353(22): 2373-83.
15. Hedegaard SS, Hvas AM, Grove EL, et al. Optical platelet aggregation versus thromboxane metabolites in healthy individuals and patients with stable coronary artery disease after low-dose aspirin administration. Thromb Res 2009; 124(1): 96-100.
16. Evangelista V, Manarini S, Di SA, et al. De novo synthesis of cyclooxygenase-1 counteracts the suppression of platelet thromboxane biosynthesis by aspirin. Circ Res 2006 Mar 17; 98(5): 593-5.
17. Michelson AD. Platelets. 2nd ed. Amsterdam: Elsevier 2007.
18. Patrono C, Rocca B. Drug insight: aspirin resistance--fact or fashion? Nat Clin Pract Cardiovasc Med 2007 Jan; 4(1): 42-50.
19. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988 Aug 13; 2(8607): 349-60.
20. Antithrombotic Trialists' Collaboration. Collaborative metaanalysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002 Jan 12; 324(7329): 71-86.
21. The Medical Research Council's General Practice Research Framework. Thrombosis prevention trial: randomised trial of lowintensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. Lancet 1998 Jan 24; 351(9098): 233-41.
22. Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative metaanalysis of individual participant data from randomised trials. Lancet 2009 May 30; 373(9678): 1849-60.
23. Mason PJ, Jacobs AK, Freedman JE. Aspirin resistance and atherothrombotic disease. J Am Coll Cardiol 2005 Sep 20; 46(6): 986-93.
24. Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR. Aspirin resistance and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ 2008 Jan 26; 336(7637): 195-8.
25. Grove EL, Kristensen SD. Update on oral antiplatelet therapy: principles, problems and promises. Future Cardiol 2009 May; 5(3): 247-58.
26. Meyer UA. Pharmacogenetics five decades of therapeutic lessons from genetic diversity. Nat Rev Genet 2004 Sep; 5(9): 669-76.
27. Nurden AT. Inherited abnormalities of platelets. Thromb Haemost 1999 Aug; 82(2): 468-80.
28. Cattaneo M. Inherited platelet-based bleeding disorders. J Thromb Haemost 2003 Jul; 1(7): 1628-36.
29. Cambria-Kiely JA, Gandhi PJ. Aspirin resistance and genetic polymorphisms. J Thromb Thrombolysis 2002 Aug; 14(1): 51-8.
30. Faraday N, Becker DM, Becker LC. Pharmacogenomics of platelet responsiveness to aspirin. Pharmacogenomics 2007 Oct; 8(10): 1413-25.
31. Goodman T, Ferro A, Sharma P. Pharmacogenetics of aspirin resistance: a comprehensive systematic review. Br J Clin Pharmacol 2008 Aug; 66(2): 222-32.
32. Feher G, Feher A, Pusch G, Lupkovics G, Szapary L, Papp E. The genetics of antiplatelet drug resistance. Clin Genet 2009 Jan; 75(1): 1-18.
33. Verschuren JJ, Trompet S, Wessels JA, et al. A systematic review on pharmacogenetics in cardiovascular disease: is it ready for clinical application? Eur Heart J 2012 Jan; 33(2): 165-75.
34. den Dunnen JT, Antonarakis SE. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 2000; 15(1): 7-12.
35. Newman PJ. Platelet alloantigens: cardiovascular as well as immunological risk factors? Lancet 1997 Feb 8; 349(9049): 370-1.
36. Coller BS, Peerschke EI, Scudder LE, Sullivan CA. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa. J Clin Invest 1983 Jul; 72(1): 325-38.
37. Kristensen SD, Wurtz M, Grove EL, et al. Contemporary use of glycoprotein IIb/IIIa inhibitors. Thromb Haemost 2012 Feb 2; 107(2): 215-24.
38. Wagner CL, Mascelli MA, Neblock DS, Weisman HF, Coller BS, Jordan RE. Analysis of GPIIb/IIIa receptor number by quantification of 7E3 binding to human platelets. Blood 1996 Aug 1; 88(3): 907-14.
39. Rosa JP, Bray PF, Gayet O, et al. Cloning of glycoprotein IIIa cDNA from human erythroleukemia cells and localization of the gene to chromosome 17. Blood 1988 Aug; 72(2): 593-600.
40. Newman PJ, Derbes RS, Aster RH. The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing. J Clin Invest 1989 May; 83(5): 1778-81.
41. Michelson AD, Furman MI, Goldschmidt-Clermont P, et al. Platelet GP IIIa Pl(A) polymorphisms display different sensitivities to agonists. Circulation 2000 Mar 7; 101(9): 1013-8.
42. Feng D, Lindpaintner K, Larson MG, et al. Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study. Arterioscler Thromb Vasc Biol 1999 Apr; 19(4): 1142-7.
43. Weiss EJ, Bray PF, Tayback M, et al. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med 1996 Apr 25; 334(17): 1090-4.
44. Carter AM, Ossei-Gerning N, Wilson IJ, Grant PJ. Association of the platelet Pl(A) polymorphism of glycoprotein IIb/IIIa and the fibrinogen Bbeta 448 polymorphism with myocardial infarction and extent of coronary artery disease. Circulation 1997 Sep 2; 96(5): 1424-31.
45. Grove EL, Orntoft TF, Lassen JF, Jensen HK, Kristensen SD. The platelet polymorphism PlA2 is a genetic risk factor for myocardial infarction. J Intern Med 2004 Jun; 255(6): 637-44.
46. Walter DH, Schachinger V, Elsner M, Dimmeler S, Zeiher AM. Platelet glycoprotein IIIa polymorphisms and risk of coronary stent thrombosis. Lancet 1997 Oct 25; 350(9086): 1217-9.
47. Kastrati A, Schomig A, Seyfarth M, et al. PlA polymorphism of platelet glycoprotein IIIa and risk of restenosis after coronary stent placement. Circulation 1999 Mar 2; 99(8): 1005-10.
48. Mikkelsson J, Perola M, Laippala P, Penttila A, Karhunen PJ. Glycoprotein IIIa Pl(A1/A2) polymorphism and sudden cardiac death. J Am Coll Cardiol 2000 Oct; 36(4): 1317-23.
49. Ardissino D, Mannucci PM, Merlini PA, et al. Prothrombotic genetic risk factors in young survivors of myocardial infarction. Blood 1999 Jul 1; 94(1): 46-51.
50. Samani NJ, Lodwick D. Glycoprotein IIIa polymorphism and risk of myocardial infarction. Cardiovasc Res 1997 Mar; 33(3): 693-7.
51. Ridker PM, Hennekens CH, Schmitz C, Stampfer MJ, Lindpaintner K. PIA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis. Lancet 1997 Feb 8; 349(9049): 385-8.
52. Mamotte CD, van Bockxmeer FM, Taylor RR. PIa1/a2 polymorphism of glycoprotein IIIa and risk of coronary artery disease and restenosis following coronary angioplasty. Am J Cardiol 1998 Jul 1; 82(1): 13-6.
53. Voora D, Horton J, Shah SH, Shaw LK, Newby LK. Polymorphisms associated with in vitro aspirin resistance are not associated with clinical outcomes in patients with coronary artery disease who report regular aspirin use. Am Heart J 2011 Jul; 162(1): 166-72.
54. Goodall AH, Curzen N, Panesar M, et al. Increased binding of fibrinogen to glycoprotein IIIa-proline33 (HPA-1b, PlA2, Zwb) positive platelets in patients with cardiovascular disease. Eur Heart J 1999 May; 20(10): 742-7.
55. Lasne D, Krenn M, Pingault V, et al. Interdonor variability of platelet response to thrombin receptor activation: influence of PlA2 polymorphism. Br J Haematol 1997 Dec; 99(4): 801-7.
56. Bennett JS, Catella-Lawson F, Rut AR, et al. Effect of the Pl(A2) alloantigen on the function of beta(3)-integrins in platelets. Blood 2001 May 15; 97(10): 3093-9.
57. Feng D, Lindpaintner K, Larson MG, et al. Platelet glycoprotein IIIa Pl(a) polymorphism, fibrinogen, and platelet aggregability: The Framingham Heart Study. Circulation 2001 Jul 10; 104(2): 140-4.
58. Cooke GE, Bray PF, Hamlington JD, Pham DM, Goldschmidt-Clermont PJ. PlA2 polymorphism and efficacy of aspirin. Lancet 1998 Apr 25; 351(9111): 1253.
59. Szczeklik A, Undas A, Sanak M, Frolow M, Wegrzyn W. Relationship between bleeding time, aspirin and the PlA1/A2 polymorphism of platelet glycoprotein IIIa. Br J Haematol 2000 Sep; 110(4): 965-7.
60. Undas A, Brummel K, Musial J, Mann KG, Szczeklik A. Pl(A2) polymorphism of beta(3) integrins is associated with enhanced thrombin generation and impaired antithrombotic action of aspirin at the site of microvascular injury. Circulation 2001 Nov 27; 104(22): 2666-72.
61. Gonzalez-Conejero R, Rivera J, Corral J, Acuna C, Guerrero JA, Vicente V. Biological assessment of aspirin efficacy on healthy individuals: heterogeneous response or aspirin failure? Stroke 2005 Feb; 36(2): 276-80.
62. Fontana P, Nolli S, Reber G, de MP. Biological effects of aspirin and clopidogrel in a randomized cross-over study in 96 healthy volunteers. J Thromb Haemost 2006 Apr; 4(4): 813-9.
63. Macchi L, Christiaens L, Brabant S, et al. Resistance in vitro to low-dose aspirin is associated with platelet PlA1 (GP IIIa) polymorphism but not with C807T(GP Ia/IIa) and C-5T Kozak (GP Ibalpha) polymorphisms. J Am Coll Cardiol 2003 Sep 17; 42(6): 1115-9.
64. Lepantalo A, Mikkelsson J, Resendiz JC, et al. Polymorphisms of COX-1 and GPVI associate with the antiplatelet effect of aspirin in coronary artery disease patients. Thromb Haemost 2006 Feb; 95(2): 253-9.
65. Cooke GE, Liu-Stratton Y, Ferketich AK, et al. Effect of platelet antigen polymorphism on platelet inhibition by aspirin, clopidogrel, or their combination. J Am Coll Cardiol 2006 Feb 7; 47(3): 541-6.
66. Bernardo E, Angiolillo DJ, Ramirez C, et al. Lack of association between gene sequence variations of platelet membrane receptors and aspirin responsiveness detected by the PFA-100 system in patients with coronary artery disease. Platelets 2006 Dec; 17(8): 586-90.
67. Kranzhofer R, Ruef J. Aspirin resistance in coronary artery disease is correlated to elevated markers for oxidative stress but not to the expression of cyclooxygenase (COX) 1/2, a novel COX-1 polymorphism or the PlA(1/2) polymorphism. Platelets 2006 May; 17(3): 163-9.
68. Lev EI, Patel RT, Guthikonda S, Lopez D, Bray PF, Kleiman NS. Genetic polymorphisms of the platelet receptors P2Y(12), P2Y(1) and GP IIIa and response to aspirin and clopidogrel. Thromb Res 2007; 119(3): 355-60.
69. Pamukcu B, Oflaz H, Nisanci Y. The role of platelet glycoprotein IIIa polymorphism in the high prevalence of in vitro aspirin resistance in patients with intracoronary stent restenosis. Am Heart J 2005 Apr; 149(4): 675-80.
70. Papp E, Havasi V, Bene J, et al. Glycoprotein IIIA gene (PlA) polymorphism and aspirin resistance: is there any correlation? Ann Pharmacother 2005 Jun; 39(6): 1013-8.
71. Lordkipanidze M, Diodati JG, Palisaitis DA, Schampaert E, Turgeon J, Pharand C. Genetic determinants of response to aspirin: Appraisal of 4 candidate genes. Thromb Res 2011 Mar; 128(1): 47-753.
72. Vijayan KV, Bray PF. Molecular mechanisms of prothrombotic risk due to genetic variations in platelet genes: Enhanced outside-in signaling through the Pro33 variant of integrin beta3. Exp Biol Med (Maywood) 2006 May; 231(5): 505-13.
73. Undas A, Sanak M, Musial J, Szczeklik A. Platelet glycoprotein IIIa polymorphism, aspirin, and thrombin generation. Lancet 1999 Mar 20; 353(9157): 982-3.
74. Andrioli G, Minuz P, Solero P, et al. Defective platelet response to arachidonic acid and thromboxane A(2) in subjects with Pl(A2) polymorphism of beta(3) subunit (glycoprotein IIIa). Br J Haematol 2000 Sep; 110(4): 911-8.
75. Morawski W, Sanak M, Cisowski M, et al. Prediction of the excessive perioperative bleeding in patients undergoing coronary artery bypass grafting: role of aspirin and platelet glycoprotein IIIa polymorphism. J Thorac Cardiovasc Surg 2005 Sep; 130(3): 791-6.
76. Stepien E, Szuldrzynski K, Branicka A, et al. [The thrombin generation is associated with the PIA1/A2 beta3, integrin polymorphism in aspirin-treated patients with coronary artery disease: a role of statins]. Pol Arch Med Wewn 2007 Jan; 117(1-2): 33-40.
77. Dropinski J, Musial J, Sanak M, Wegrzyn W, Nizankowski R, Szczeklik A. Antithrombotic effects of aspirin based on PLA1/A2 glycoprotein IIIa polymorphism in patients with coronary artery disease. Thromb Res 2007; 119(3): 301-3.
78. Lim E, Carballo S, Cornelissen J, et al. Dose-related efficacy of aspirin after coronary surgery in patients With Pl(A2) polymorphism (NCT00262275). Ann Thorac Surg 2007 Jan; 83(1): 134-8.
79. Abderrazek F, Chakroun T, Addad F, et al. The GPIIIa PlA polymorphism and the platelet hyperactivity in Tunisian patients with stable coronary artery disease treated with aspirin. Thromb Res 2010 Jun; 125(6): e265-e268.
80. Santoro SA, Zutter MM. The alpha 2 beta 1 integrin: a collagen receptor on platelets and other cells. Thromb Haemost 1995 Sep; 74(3): 813-21.
81. Heemskerk JW, Siljander P, Vuist WM, et al. Function of glycoprotein VI and integrin alpha2beta1 in the procoagulant response of single, collagen-adherent platelets. Thromb Haemost 1999 May; 81(5): 782-92.
82. Carlsson LE, Santoso S, Spitzer C, Kessler C, Greinacher A. The alpha2 gene coding sequence T807/A873 of the platelet collagen receptor integrin alpha2beta1 might be a genetic risk factor for the development of stroke in younger patients. Blood 1999 Jun 1; 93(11): 3583-6.
83. Moshfegh K, Wuillemin WA, Redondo M, et al. Association of two silent polymorphisms of platelet glycoprotein Ia/IIa receptor with risk of myocardial infarction: a case-control study. Lancet 1999 Jan 30; 353(9150): 351-4.
84. Santoso S, Kunicki TJ, Kroll H, Haberbosch W, Gardemann A. Association of the platelet glycoprotein Ia C807T gene polymorphism with nonfatal myocardial infarction in younger patients. Blood 1999 Apr 15; 93(8): 2449-53.
85. Roest M, Banga JD, Grobbee DE, et al. Homozygosity for 807 T polymorphism in alpha(2) subunit of platelet alpha(2)beta(1) is associated with increased risk of cardiovascular mortality in high-risk women. Circulation 2000 Oct 3; 102(14): 1645-50.
86. Croft SA, Hampton KK, Sorrell JA, et al. The GPIa C807T dimorphism associated with platelet collagen receptor density is not a risk factor for myocardial infarction. Br J Haematol 1999 Sep; 106(3): 771-6.
87. Morita H, Kurihara H, Imai Y, et al. Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and myocardial infarction in Japanese. An approach entailing melting curve analysis with specific fluorescent hybridization probes. Thromb Haemost 2001 Feb; 85(2): 226-30.
88. Tsantes AE, Nikolopoulos GK, Bagos PG, Vaiopoulos G, Travlou A. Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and coronary artery disease: a meta-analysis. Int J Cardiol 2007 May 31; 118(2): 189-96.
89. Nikolopoulos GK, Tsantes AE, Bagos PG, Travlou A, Vaiopoulos G. Integrin, alpha 2 gene C807T polymorphism and risk of ischemic stroke: a meta-analysis. Thromb Res 2007; 119(4): 501-10.
90. Su G, Wang Z, Ding Y. Association of the platelet membrane glycoprotein I a C807T gene polymorphism with aspirin resistance. J Huazhong Univ Sci Technolog Med Sci 2007 Dec; 27(6): 664-7.
91. Croft SA, Samani NJ, Teare MD, et al. Novel platelet membrane glycoprotein VI dimorphism is a risk factor for myocardial infarction. Circulation 2001 Sep 25; 104(13): 1459-63.
92. Ollikainen E, Mikkelsson J, Perola M, Penttila A, Karhunen PJ. Platelet membrane collagen receptor glycoprotein VI polymorphism is associated with coronary thrombosis and fatal myocardial infarction in middle-aged men. Atherosclerosis 2004 Sep; 176(1): 95-9.
93. Kunicki TJ, Williams SA, Nugent DJ, et al. Lack of association between aspirin responsiveness and seven candidate gene haplotypes in patients with symptomatic vascular disease. Thromb Haemost 2009 Jan; 101(1): 123-33.
94. Bonnefoy A, Vermylen J, Hoylaerts MF. Inhibition of von Willebrand factor-GPIb/IX/V interactions as a strategy to prevent arterial thrombosis. Expert Rev Cardiovasc Ther 2003 Jul; 1(2): 257-69.
95. Gonzalez-Conejero R, Lozano ML, Rivera J, et al. Polymorphisms of platelet membrane glycoprotein Ib associated with arterial thrombotic disease. Blood 1998 Oct 15; 92(8): 2771-6.
96. Murata M, Matsubara Y, Kawano K, et al. Coronary artery disease and polymorphisms in a receptor mediating shear stress-dependent platelet activation. Circulation 1997 Nov 18; 96(10): 3281-6.
97. Mikkelsson J, Perola M, Penttila A, Karhunen PJ. Platelet glycoprotein Ibalpha HPA-2 Met/VNTR B haplotype as a genetic predictor of myocardial infarction and sudden cardiac death. Circulation 2001 Aug 21; 104(8): 876-80.
98. Afshar-Kharghan V, Matijevic-Aleksic N, Ahn C, Boerwinkle E, Wu KK, Lopez JA. The variable number of tandem repeat polymorphism of platelet glycoprotein Ibalpha and risk of coronary heart disease. Blood 2004 Feb 1; 103(3): 963-5.
99. Sperr WR, Huber K, Roden M, et al. Inherited platelet glycoprotein polymorphisms and a risk for coronary heart disease in young central Europeans. Thromb Res 1998 May 1; 90(3): 117-23.
100. Douglas H, Michaelides K, Gorog DA, et al. Platelet membrane glycoprotein Ibalpha gene -5T/C Kozak sequence polymorphism as an independent risk factor for the occurrence of coronary thrombosis. Heart 2002 Jan; 87(1): 70-4.
101. Cervera A, Tassies D, Obach V, Amaro S, Reverter JC, Chamorro A. The BC genotype of the VNTR polymorphism of platelet glycoprotein Ibalpha is overrepresented in patients with recurrent stroke regardless of aspirin therapy. Cerebrovasc Dis 2007; 24(2-3): 242-6.
102. Afshar-Kharghan V, Li CQ, Khoshnevis-Asl M, Lopez JA. Kozak sequence polymorphism of the glycoprotein (GP) Ibalpha gene is a major determinant of the plasma membrane levels of the platelet GP Ib-IX-V complex. Blood 1999 Jul 1; 94(1): 186-91.
103. Douglas H, Davies GJ, Michaelides K, et al. Detection of functional differences between different platelet membrane glycoprotein Ibalpha variable number tandem repeat and Kozak genotypes as shown by the PFA-100 system. Heart 2006 May; 92(5): 676-8.
104. Croft SA, Hampton KK, Daly ME, Steeds RP, Channer KS, Samani NJ. Kozak sequence polymorphism in the platelet GPIbalpha gene is not associated with risk of myocardial infarction. Blood 2000 Mar 15; 95(6): 2183-4.
105. Kunicki TJ, Williams SA, Salomon DR, et al. Genetics of platelet reactivity in normal, healthy individuals. J Thromb Haemost 2009 Dec; 7(12): 2116-22.
106. Fujiwara T, Ikeda M, Esumi K, et al. Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity. Pharmacogenomics J 2007 Dec; 7(6): 395-403.
107. Hillarp A, Palmqvist B, Lethagen S, Villoutreix BO, Mattiasson I. Mutations within the cyclooxygenase-1 gene in aspirin nonresponders with recurrence of stroke. Thromb Res 2003; 112(5-6): 275-83.
108. Halushka MK, Walker LP, Halushka PV. Genetic variation in cyclooxygenase 1: effects on response to aspirin. Clin Pharmacol Ther 2003 Jan; 73(1): 122-30.
109. Maree AO, Curtin RJ, Chubb A, et al. Cyclooxygenase-1 haplotype modulates platelet response to aspirin. J Thromb Haemost 2005 Oct; 3(10): 2340-5.
110. Faraday N, Yanek LR, Mathias R, et al. Heritability of platelet responsiveness to aspirin in activation pathways directly and indirectly related to cyclooxygenase-1. Circulation 2007 May 15; 115(19): 2490-6.
111. Lee CR, North KE, Bray MS, Couper DJ, Heiss G, Zeldin DC. Cyclooxygenase polymorphisms and risk of cardiovascular events: the Atherosclerosis Risk in Communities (ARIC) study. Clin Pharmacol Ther 2008 Jan; 83(1): 52-60.
112. Takahashi S, Ushida M, Komine R, et al. Platelet responsiveness to in vitro aspirin is independent of COX-1 and COX-2 protein levels and polymorphisms. Thromb Res 2008; 121(4): 509-17.
113. Censarek P, Steger G, Paolini C, et al. Alternative splicing of platelet cyclooxygenase-2 mRNA in patients after coronary artery bypass grafting. Thromb Haemost 2007 Dec; 98(6): 1309-15.
114. Cipollone F, Toniato E, Martinotti S, et al. A polymorphism in the cyclooxygenase 2 gene as an inherited protective factor against myocardial infarction and stroke. JAMA 2004 May 12; 291(18): 2221-8.
115. Storey RF. Biology and pharmacology of the platelet P2Y12 receptor. Curr Pharm Des 2006; 12(10): 1255-9.
116. Hetherington SL, Singh RK, Lodwick D, Thompson JR, Goodall AH, Samani NJ. Dimorphism in the P2Y1 ADP receptor gene is associated with increased platelet activation response to ADP. Arterioscler Thromb Vasc Biol 2005 Jan; 25(1): 252-7.
117. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996 Nov 16; 348(9038): 1329-39.
118. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001 Aug 16; 345(7): 494-502.
119. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007 Nov 15; 357(20): 2001-15.
120. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009 Sep 10; 361(11): 1045-57.
121. Andre P, LaRocca T, Delaney SM, et al. Anticoagulants (thrombin inhibitors) and aspirin synergize with P2Y12 receptor antagonism in thrombosis. Circulation 2003 Nov 25; 108(21): 2697-703.
122. Jefferson BK, Foster JH, McCarthy JJ, et al. Aspirin resistance and a single gene. Am J Cardiol 2005 Mar 15; 95(6): 805-8.
123. Li Q, Chen BL, Ozdemir V, et al. Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin. Pharmacogenomics 2007 Jun; 8(6): 577-86.
124. Bierend A, Rau T, Maas R, Schwedhelm E, Boger RH. P2Y12 polymorphisms and antiplatelet effects of aspirin in patients with coronary artery disease. Br J Clin Pharmacol 2008 Apr; 65(4): 540-7.
125. Fontana P, Dupont A, Gandrille S, et al. Adenosine diphosphateinduced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects. Circulation 2003 Aug 26; 108(8): 989-95.
126. Fontana P, Gaussem P, Aiach M, Fiessinger JN, Emmerich J, Reny JL. P2Y12 H2 haplotype is associated with peripheral arterial disease: a case-control study. Circulation 2003 Dec 16; 108(24): 2971-3.
127. Higuchi W, Fuse I, Hattori A, Aizawa Y. Mutations of the platelet thromboxane A2 (TXA2) receptor in patients characterized by the absence of TXA2-induced platelet aggregation despite normal TXA2 binding activity. Thromb Haemost 1999 Nov; 82(5): 1528-31.
128. Postula M, Kaplon-Cieslicka A, Rosiak M, et al. Genetic determinants of platelet reactivity during acetylsalicylic acid therapy in diabetic patients: evaluation of 27 polymorphisms within candidate genes. J Thromb Haemost 2011 Nov; 9(11): 2291-301.
129. Fontana P, Gandrille S, Remones V, et al. Identification of functional polymorphisms of the thromboxane A2 receptor gene in healthy volunteers. Thromb Haemost 2006 Sep; 96(3): 356-60.
130. Lorand L. Factor XIII: structure, activation, and interactions with fibrinogen and fibrin. Ann N Y Acad Sci 2001; 936: 291-311.
131. Kohler HP, Stickland MH, Ossei-Gerning N, Carter A, Mikkola H, Grant PJ. Association of a common polymorphism in the factor XIII gene with myocardial infarction. Thromb Haemost 1998 Jan; 79(1): 8-13.
132. Catto AJ, Kohler HP, Coore J, Mansfield MW, Stickland MH, Grant PJ. Association of a common polymorphism in the factor XIII gene with venous thrombosis. Blood 1999 Feb 1; 93(3): 906-8.
133. Catto AJ, Kohler HP, Bannan S, Stickland M, Carter A, Grant PJ. Factor XIII Val 34 Leu: a novel association with primary intracerebral hemorrhage. Stroke 1998 Apr; 29(4): 813-6.
134. Ariens RA, Lai TS, Weisel JW, Greenberg CS, Grant PJ. Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms. Blood 2002 Aug 1; 100(3): 743-54.
135. Undas A, Undas R, Musial J, Szczeklik A. A low dose of aspirin (75 mg/day) lowers thrombin generation to a similar extent as a high dose of aspirin (300 mg/day). Blood Coagul Fibrinolysis 2000 Apr; 11(3): 231-4.
136. Undas A, Brummel-Ziedins KE, Mann KG. Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions. Blood 2007 Mar 15; 109(6): 2285-92.
137. Undas A, Sydor WJ, Brummel K, Musial J, Mann KG, Szczeklik A. Aspirin alters the cardioprotective effects of the factor XIII Val34Leu polymorphism. Circulation 2003 Jan 7; 107(1): 17-20.
138. Pamukcu B, Oflaz H, Onur I, Hancer V, Yavuz S, Nisanci Y. Impact of genetic polymorphisms on platelet function and aspirin resistance. Blood Coagul Fibrinolysis 2010 Jan; 21(1): 53-6.
139. Levy G. Pharmacokinetics of salicylate in man. Drug Metab Rev 1979; 9(1): 3-19.
140. Ciotti M, Marrone A, Potter C, Owens IS. Genetic polymorphism in the human UGT1A6 (planar phenol) UDPglucuronosyltransferase: pharmacological implications. Pharmacogenetics 1997 Dec; 7(6): 485-95.
141. Bigler J, Whitton J, Lampe JW, Fosdick L, Bostick RM, Potter JD. CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk. Cancer Res 2001 May 1; 61(9): 3566-9.
142. Chan AT, Tranah GJ, Giovannucci EL, Hunter DJ, Fuchs CS. Genetic variants in the UGT1A6 enzyme, aspirin use, and the risk of colorectal adenoma. J Natl Cancer Inst 2005 Mar 16; 97(6): 457-60.
143. Hubner RA, Muir KR, Liu JF, et al. Genetic variants of UGT1A6 influence risk of colorectal adenoma recurrence. Clin Cancer Res 2006 Nov 1; 12(21): 6585-9.
144. Chen Y, Kuehl GE, Bigler J, et al. UGT1A6 polymorphism and salicylic acid glucuronidation following aspirin. Pharmacogenet Genomics 2007 Aug; 17(8): 571-9.
145. van Oijen MG, Barthelemy C, Janssen MJ, et al. Effect of genetic polymorphisms in UDP-glucuronosyltransferase 1A6 (UGT1A6) on acetylsalicylic acid metabolism in healthy female volunteers. Pharmacology 2009; 83(4): 237-42.
146. Navarro SL, Saracino MR, Makar KW, et al. Determinants of aspirin metabolism in healthy men and women: effects of dietary inducers of UDP-glucuronosyltransferases. J Nutrigenet Nutrigenomics 2011; 4(2): 110-8.
147. Imaizumi TA, Stafforini DM, Yamada Y, McIntyre TM, Prescott SM, Zimmerman GA. Platelet-activating factor: a mediator for clinicians. J Intern Med 1995 Jul; 238(1): 5-20.
148. Stafforini DM. Biology of platelet-activating factor acetylhydrolase (PAF-AH, lipoprotein associated phospholipase A2). Cardiovasc Drugs Ther 2009 Feb; 23(1): 73-83.
149. Ninio E, Tregouet D, Carrier JL, et al. Platelet-activating factoracetylhydrolase and PAF-receptor gene haplotypes in relation to future cardiovascular event in patients with coronary artery disease. Hum Mol Genet 2004 Jul 1; 13(13): 1341-51.
150. Kruse S, Mao XQ, Heinzmann A, et al. The Ile198Thr and Ala379Val variants of plasmatic PAF-acetylhydrolase impair catalytical activities and are associated with atopy and asthma. Am J Hum Genet 2000 May; 66(5): 1522-30.
151. Casas JP, Ninio E, Panayiotou A, et al. PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry. Circulation 2010 Jun 1; 121(21): 2284-93.
152. Lopez AD, Murray CC. The global burden of disease, 1990-2020. Nat Med 1998 Nov; 4(11): 1241-3.
153. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006 May 27; 367(9524): 1747-57.
154. Soranzo N, Rendon A, Gieger C, et al. A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function. Blood 2009 Apr 16; 113(16): 3831-7.
155. Soranzo N, Spector TD, Mangino M, et al. A genome-wide metaanalysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Nat Genet 2009 Nov; 41(11): 1182-90.
156. Monaco C, Mathur A, Martin JF. What causes acute coronary syndromes? Applying Koch's postulates. Atherosclerosis 2005 Mar; 179(1): 1-15.
157. Lordkipanidze M, Pharand C, Schampaert E, Turgeon J, Palisaitis DA, Diodati JG. A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease. Eur Heart J 2007 Jul; 28(14): 1702-8.
158. Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, ten Berg JM, Hackeng CM. High on-aspirin platelet reactivity as measured with aggregation-based, cyclooxygenase-1 inhibition sensitive platelet function tests is associated with the occurrence of atherothrombotic events. J Thromb Haemost 2010 Oct; 8(10): 2140-8.
159. Grove EL, Hvas AM, Johnsen HL, et al. A comparison of platelet function tests and thromboxane metabolites to evaluate aspirin response in healthy individuals and patients with coronary artery disease. Thromb Haemost 2010 Jun; 103(6): 1245-53.
160. Kuliczkowski W, Witkowski A, Polonski L, et al. Interindividual variability in the response to oral antiplatelet drugs: a position paper of the Working Group on antiplatelet drugs resistance appointed by the Section of Cardiovascular Interventions of the Polish Cardiac Society, endorsed by the Working Group on Thrombosis of the European Society of Cardiology. Eur Heart J 2009 Feb; 30(4): 426-35.
161. Feher G, Koltai K, Papp E, et al. Aspirin resistance: possible roles of cardiovascular risk factors, previous disease history, concomitant medications and haemorrheological variables. Drugs Aging 2006; 23(7): 559-67.
162. Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 2001 Dec 20; 345(25): 1809-17.
163. Kurth T, Glynn RJ, Walker AM, et al. Inhibition of clinical benefits of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs. Circulation 2003 Sep 9; 108(10): 1191-5.
164. Malinin AI, Ong S, Makarov LM, Petukhova EY, Serebruany VL. Platelet inhibition beyond conventional antiplatelet agents: expanding role of angiotensin receptor blockers, statins and selective serotonin reuptake inhibitors. Int J Clin Pract 2006 Aug; 60(8): 993-1002.
165. Wurtz M, Grove EL, Kristensen SD, Hvas AM. The antiplatelet effect of aspirin is reduced by proton pump inhibitors in patients with coronary artery disease. Heart 2010 Mar; 96(5): 368-71.
166. Charlot M, Grove EL, Hansen PR, et al. Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study. BMJ 2011; 342: d2690.
167. Shankar H, Garcia A, Prabhakar J, Kim S, Kunapuli SP. P2Y12 receptor-mediated potentiation of thrombin-induced thromboxane A2 generation in platelets occurs through regulation of Erk1/2 activation. J Thromb Haemost 2006 Mar; 4(3): 638-47.
168. Hobson AR, Qureshi Z, Banks P, Curzen NP. Effects of clopidogrel on aspirin specific pathways of platelet inhibition. Platelets 2009 Sep; 20(6): 386-90.
169. Armstrong PC, Dhanji AR, Tucker AT, Mitchell JA, Warner TD. Reduction of platelet thromboxane A2 production ex vivo and in vivo by clopidogrel therapy. J Thromb Haemost 2010 Mar; 8(3): 613-5.
170. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001 Mar 15; 344(11): 783-92.
171. Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008 Oct 23; 359(17): 1757-65.
172. Hulot JS, Bura A, Villard E, et al. Cytochrome P450 2C19 loss-offunction polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 2006 Oct 1; 108(7): 2244-7.
173. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 2009 Jan 22; 360(4): 354-62.
174. Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet 2009 Jan 24; 373(9660): 309-17.
175. Sibbing D, Stegherr J, Latz W, et al. Cytochrome P450 2C19 lossof-function polymorphism and stent thrombosis following percutaneous coronary intervention. Eur Heart J 2009 Apr; 30(8): 916-22.
176. Giusti B, Gori AM, Marcucci R, et al. Relation of cytochrome P450 2C19 loss-of-function polymorphism to occurrence of drugeluting coronary stent thrombosis. Am J Cardiol 2009 Mar 15; 103(6): 806-11.
177. Brandt JT, Payne CD, Wiviott SD, et al. A comparison of prasugrel and clopidogrel loading doses on platelet function: magnitude of platelet inhibition is related to active metabolite formation. Am Heart J 2007 Jan; 153(1): 66-16.
178. Brandt JT, Close SL, Iturria SJ, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost 2007 Dec; 5(12): 2429-36.
179. Wallentin L, James S, Storey RF, et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet 2010 Oct 16; 376(9749): 1320-8.
180. Tirnaksiz E, Pamukcu B, Oflaz H, Nisanci Y. Effect of high dose statin therapy on platelet function; statins reduce aspirin-resistant platelet aggregation in patients with coronary heart disease. J Thromb Thrombolysis 2009 Jan; 27(1): 24-8.
181. Weinshilboum R. Inheritance and drug response. N Engl J Med 2003 Feb 6; 348(6): 529-37.