Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000077.xml
Semin Thromb Hemost 2004; 30(5): 591-600
DOI: 10.1055/s-2004-835679
DOI: 10.1055/s-2004-835679
Clinical and Functional Consequences of Platelet Membrane Glycoprotein Polymorphisms
Donald L. Yee 1 , Paul F. Bray2Further Information
Publication History
Publication Date:
21 October 2004 (online)
The last several years have seen an abundance of studies of genetic risk factors for vascular disease, and platelet glycoprotein (GP) polymorphisms have been a primary focus of this area of research. This article reviews GP receptor polymorphisms, particularly those on GPIa-IIa (integrin α2β1), GPIb-IX-V, GPIIb-IIIa (integrin αIIbβ3), and GPVI, and summarizes clinical and functional studies that have attempted to clarify their roles in human disease. Our focus is on recent work relevant to thrombotic and hemostatic processes and advances in pharmacogenetics. We consider issues affecting our ability to derive firm conclusions from these studies, and discuss future directions in this rapidly evolving area.
KEYWORDS
Glycoprotein polymorphisms - platelet reactivity - thrombosis - pharmacogenetics
REFERENCES
- 1 Afshar-Kharghan V, Bray P F. Platelet polymorphisms. In: Michelson AD Platelets Academic Press 2002: 157-169
- 2 Bray P F. Platelet glycoprotein polymorphisms as risk factors for thrombosis. Curr Opin Hematol. 2000; 7 284-289
- 3 Bussel J B, Kunicki T J, Michelson A D. Platelets: New Understanding of Platelet Glycoproteins and Their Role in Disease. Hematology Washington, DC; American Society of Hematology 2000: 222-240
- 4 Reiner A P, Siscovick D S, Rosendaal F R. Platelet glycoprotein gene polymorphisms and risk of thrombosis: facts and fancies. Rev Clin Exp Hematol. 2001; 5 262-287
- 5 Furman M I, Benoit S E, Barnard M R et al.. Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease. J Am Coll Cardiol. 1998; 31 352-358
- 6 Kabbani S S, Watkins M W, Ashikaga T et al.. Platelet reactivity characterized prospectively: a determinant of outcome 90 days after percutaneous coronary intervention. Circulation. 2001; 104 181-186
- 7 Trip M D, Cats V M, van Capelle F J, Vreeken J. Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med. 1990; 322 1549-1554
- 8 Wood J, Dong J F, Yee D L et al.. Evaluating platelet hyperreactivity for arterial thrombosis risk. Blood. 2003; 102 93A
- 9 Weiss E J, Bray P F, Tayback M et al.. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med. 1996; 334 1090-1094
- 10 Clemetson K J, Clemetson J M. Platelet collagen receptors. Thromb Haemost. 2001; 86 189-197
- 11 Moshfegh K, Wuillemin W A, 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; 353 351-354
- 12 Casorelli I, De Stefano V, Leone A M et al.. The C807T/G873A polymorphism in the platelet glycoprotein Ia gene and the risk of acute coronary syndrome in the Italian population. Br J Haematol. 2001; 114 150-154
- 13 Roest M, Banga J D, Grobbee D E 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; 102 1645-1650
- 14 Santoso S, Kunicki T J, Kroll H, Haberbosch W, Gardemann A. Association of the platelet glycoprotein Ia C807T gene polymorphism with nonfatal myocardial infarction in younger patients. Blood. 1999; 93 2449-2453
- 15 Meisel C, Cascorbi I, Herrmann A et al.. The platelet glycoprotein Ia C807T polymorphism as risk factor for coronary catheter interventions. Blood. 2000; 96 2002-2003
- 16 von Beckerath N, Koch W, Mehilli J et al.. Glycoprotein Ia gene C807T polymorphism and risk for major adverse cardiac events within the first 30 days after coronary artery stenting. Blood. 2000; 95 3297-3301
- 17 Carlsson L E, Santoso S, Spitzer C, Kessler C, Greinacher A. The alpha 2 gene coding sequence T807/A873 of the platelet collagen receptor integrin alpha 2beta 1 might be a genetic risk factor for the development of stroke in younger patients. Blood. 1999; 93 3583-3586
- 18 Reiner A P, Kumar P N, Schwartz S M et al.. Genetic variants of platelet glycoprotein receptors and risk of stroke in young women. Stroke. 2000; 31 1628-1633
- 19 Kunicki T J, Kritzik M, Annis D S, Nugent D J. Hereditary variation in platelet integrin alpha 2 beta 1 density is associated with two silent polymorphisms in the alpha 2 gene coding sequence. Blood. 1997; 89 1939-1943
- 20 Kritzik M, Savage B, Nugent D J et al.. Nucleotide polymorphisms in the alpha2 gene define multiple alleles that are associated with differences in platelet alpha2 beta1 density. Blood. 1998; 92 2382-2388
- 21 Corral J, Gonzalez-Conejero R, Rivera J et al.. Role of the 807 C/T polymorphism of the alpha2 gene in platelet GP Ia collagen receptor expression and function-effect in thromboembolic diseases. Thromb Haemost. 1999; 81 951-956
- 22 Jacquelin B, Rozenshteyn D, Kanaji S et al.. Characterization of inherited differences in transcription of the human integrin alpha 2 gene. J Biol Chem. 2001; 276 23518-23524
- 23 Lopez J A, Dong J F. Structure and function of the glycoprotein Ib-IX-V complex. Curr Opin Hematol. 1997; 4 323-329
- 24 Coller B S, Peerschke E I, Scudder L E, Sullivan C A. Studies with a murine monoclonal antibody that abolishes ristocetin-induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor. Blood. 1983; 61 99-110
- 25 Yamamoto N, Kitagawa H, Tanoue K, Yamazaki H. Monoclonal antibody to glycoprotein Ib inhibits both thrombin- and ristocetin-induced platelet aggregations. Thromb Res. 1985; 39 751-759
- 26 Dormann D, Clemetson K J, Kehrel B E. The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity. Blood. 2000; 96 2469-2478
- 27 Afshar-Kharghan V, Matijevic-Aleksic N, Ahn C et al.. The variable number of tandem repeat polymorphism of platelet glycoprotein Ib{alpha} and risk of coronary heart disease. Blood. 2004; 103 963-965
- 28 Baker R I, Eikelboom J, Lofthouse E et al.. Platelet glycoprotein Ib{alpha} Kozak polymorphism is associated with an increased risk of ischemic stroke. Blood. 2001; 98 36-40
- 29 Gonzalez-Conejero R, Lozano M L, Rivera J et al.. Polymorphisms of platelet membrane glycoprotein Ibalpha associated with arterial thrombotic disease. Blood. 1998; 92 2771-2776
- 30 Kenny D, Muckian C, Fitzgerald D J, Cannon C P, Shields D C. Platelet glycoprotein Ib alpha receptor polymorphisms and recurrent ischaemic events in acute coronary syndrome patients. J Thromb Thrombolysis. 2002; 13 13-19
- 31 Mikkelsson J, Perola M, Penttila A, Karhunen P J. Platelet glycoprotein Ib{alpha} HPA-2 Met/VNTR B haplotype as a genetic predictor of myocardial infarction and sudden cardiac death. Circulation. 2001; 104 876-880
- 32 Murata M, Matsubara Y, Kawano K et al.. Coronary artery disease and polymorphisms in a receptor mediating shear stress-dependent platelet activation. Circulation. 1997; 96 3281-3286
- 33 Sonoda A, Murata M, Ikeda Y, Fukuuchi Y, Watanabe K. Stroke and platelet glycoprotein Ibalpha polymorphisms. Thromb Haemost. 2001; 85 573-574
- 34 Sonoda A, Murata M, Ito D et al.. Association between platelet glycoprotein Ib{alpha} genotype and ischemic cerebrovascular disease. Stroke. 2000; 31 493-497
- 35 Ulrichts H, Vanhoorelbeke K, Cauwenberghs S et al.. Von Willebrand factor but not {alpha}-thrombin binding to platelet glycoprotein ib{alpha} is influenced by the HPA-2 polymorphism. Arterioscler Thromb Vasc Biol. 2003; 23 1302-1307
- 36 Yee D L, Wood J, Bergeron A et al.. Thr-145 and VNTR C/D polymorphisms on glycoprotein Iba demonstrate increased platelet reactivity to shear stress and ristocetin. Blood. 2003; 102 783A
- 37 Corral J, Lozano M L, Gonzalez-Conejero R et al.. A common polymorphism flanking the ATG initiator codon of GPIb alpha does not affect expression and is not a major risk factor for arterial thrombosis. Thromb Haemost. 2000; 83 23-28
- 38 Afshar-Kharghan V, Li C Q, Khoshnevis-Asl M, Lopez J A. 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; 94 186-191
- 39 Newman P J, Derbes R S, Aster R H. 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; 83 1778-1781
- 40 Marian A J, Brugada R, Kleiman N S. Platelet glycoprotein IIIa PlA polymorphism and myocardial infarction. N Engl J Med. 1996; 335 1071-1072
- 41 Bray P F, Weiss E J, Tayback M, Goldschmidt-Clermont P J. PlA1/A2 polymorphism of platelet glycoprotein IIIa and risk of cardiovascular disease. Lancet. 1997; 349 1100-1101
- 42 Ridker P M, Stampfer M J. Assessment of genetic markers for coronary thrombosis: promise and precaution. Lancet. 1999; 353 687-688
- 43 Mikkelsson J, Perola M, Laippala P et al.. Glycoprotein IIIa PlA polymorphism associates with progression of coronary artery disease and with myocardial infarction in an autopsy series of middle-aged men who died suddenly. Arterioscler Thromb Vasc Biol. 1999; 19 2573-2578
- 44 Mikkelsson J, Perola M, Laippala P, Penttila A, Karhunen P J. Glycoprotein IIIa Pl(A1/A2) polymorphism and sudden cardiac death. J Am Coll Cardiol. 2000; 36 1317-1323
- 45 Walter D H, Schachinger V, Elsner M, Dimmeler S, Zeiher A M. Platelet glycoprotein IIIa polymorphisms and risk of coronary stent thrombosis. Lancet. 1997; 350 1217-1219
- 46 Kastrati A, Schomig A, Seyfarth M et al.. PlA polymorphism of platelet glycoprotein IIIa and risk of restenosis after coronary stent placement. Circulation. 1999; 99 1005-1010
- 47 Zotz R B, Klein M, Dauben H P et al.. Prospective analysis after coronary-artery bypass grafting: platelet GP IIIa polymorphism (HPA-1b/PIA2) is a risk factor for bypass occlusion, myocardial infarction, and death. Thromb Haemost. 2000; 83 404-407
- 48 Di Castelnuovo A, de Gaetano G, Donati M B, Iacoviello L. Platelet glycoprotein receptor IIIa polymorphism PLA1/PLA2 and coronary risk: a meta-analysis. Thromb Haemost. 2001; 85 626-633
- 49 Wu A H, Tsongalis G J. Correlation of polymorphisms to coagulation and biochemical risk factors for cardiovascular diseases. Am J Cardiol. 2001; 87 1361-1366
- 50 Boekholdt S M, Peters R J, de Maat M P et al.. Interaction between a genetic variant of the platelet fibrinogen receptor and fibrinogen levels in determining the risk of cardiovascular events. Am Heart J. 2004; 147 181-186
- 51 Bojesen S E, Tybjaerg-Hansen A, Nordestgaard B G. Integrin {beta}3 Leu33Pro homozygosity and risk of cancer. J Natl Cancer Inst. 2003; 95 1150-1157
- 52 Tschoepe D, Menart B, Ferber P et al.. Genetic variation of the platelet- surface integrin GPIIb-IIIa (PIA1/A2-SNP) shows a high association with Type 2 diabetes mellitus. Diabetologia. 2003; 46 984-989
- 53 Michelson A D, Furman M I, Goldschmidt-Clermont P et al.. Platelet GP IIIa Pl(A) polymorphisms display different sensitivities to agonists. Circulation. 2000; 101 1013-1018
- 54 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; 99 801-807
- 55 Bennett J S, Catella-Lawson F, Rut A R et al.. Effect of the PlA2 alloantigen on the function of {beta}3-integrins in platelets. Blood. 2001; 97 3093-3099
- 56 Vijayan K V, Goldschmidt-Clermont P J, Roos C, Bray P F. The PlA2 polymorphism of integrin {beta}3 enhances outside-in signaling and adhesive functions. J Clin Invest. 2000; 105 793-802
- 57 Vijayan K V, Liu Y, Sun C, Bray P F. The Pro33 isoform of integrin beta3 enhances outside-in signaling by regulating the activation of serine/threonine phosphatases. Blood. 2003; 102 161A
- 58 Vijayan K V, Huang T C, Liu Y et al.. Shear stress augments the enhanced adhesive phenotype of cells expressing the Pro33 isoform of integrin beta3. FEBS Lett. 2003; 540 41-46
- 59 Croft S A, Samani N J, Teare M D et al.. Novel platelet membrane glycoprotein VI dimorphism is a risk factor for myocardial infarction. Circulation. 2001; 104 1459-1463
- 60 Takagi S, Iwai N, Baba S et al.. A GPVI polymorphism is a risk factor for myocardial infarction in Japanese. Atherosclerosis. 2002; 165 397-398
- 61 Cole V J, Staton J M, Eikelboom J W et al.. Collagen platelet receptor polymorphisms integrin alpha2beta1 C807T and GPVI Q317L and risk of ischemic stroke. J Thromb Haemost. 2003; 1 963-970
- 62 Furihata K, Clemetson K J, Deguchi H, Kunicki T J. Variation in human platelet glycoprotein VI content modulates glycoprotein VI-specific prothrombinase activity. Arterioscler Thromb Vasc Biol. 2001; 21 1857-1863
- 63 Chen H, Locke D, Liu Y, Liu C, Kahn M L. The platelet receptor GPVI mediates both adhesion and signaling responses to collagen in a receptor density-dependent fashion. J Biol Chem. 2002; 277 3011-3019
- 64 Best D, Senis Y A, Jarvis G E et al.. GPVI levels in platelets: relationship to platelet function at high shear. Blood. 2003; 102 2811-2818
- 65 Joutsi-Korhonen L, Smethurst P A, Rankin A et al.. The low-frequency allele of the platelet collagen signaling receptor glycoprotein VI is associated with reduced functional responses and expression. Blood. 2003; 101 4372-4379
- 66 Ridker P M, Hennekens C H, Schmitz C, Stampfer M J, Lindpaintner K. PIA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis. Lancet. 1997; 349 385-388
- 67 Di Paola J, Federici A B, Mannucci P M et al.. Low platelet alpha 2beta 1 levels in type I von Willebrand disease correlate with impaired platelet function in a high shear stress system. Blood. 1999; 93 3578-3582
- 68 Ghosh K, Kulkarni B, Nair S, Shetty S, Mohanty D. Human platelet alloantigen polymorphism in Glanzmann’s thrombasthenia and its impact on the severity of the disease. Br J Haematol. 2002; 119 348-353
- 69 Pereira J, Quiroga T, Pereira M E et al.. Platelet membrane glycoprotein polymorphisms do not influence the clinical expressivity of von Willebrand disease type 1. Thromb Haemost. 2003; 90 1135-1140
- 70 Gum P A, Kottke-Marchant K, Poggio E D et al.. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol. 2001; 88 230-235
- 71 Buchanan M R, Brister S J. Individual variation in the effects of ASA on platelet function: implications for the use of ASA clinically. Can J Cardiol. 1995; 11 221-227
- 72 Steinhubl S R, Varanasi J S, Goldberg L, Varinasi J S. Determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol. 2003; 42 1336-1337
- 73 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; 110 911-918
- 74 Undas A, Brummel K, Musial J, Mann K G, 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; 104 2666-2672
- 75 Bihour C, Durrieu-Jais C, Macchi L et al.. Expression of markers of platelet activation and the interpatient variation in response to abciximab. Arterioscler Thromb Vasc Biol. 1999; 19 212-219
- 76 Holmes M B, Sobel B E, Schneider D J. Variable responses to inhibition of fibrinogen binding induced by tirofiban and eptifibatide in blood from healthy subjects. Am J Cardiol. 1999; 84 203-207
- 77 Rozalski M, Watala C. Antagonists of platelet fibrinogen receptor are less effective in carriers of Pl(A2) polymorphism of beta(3) integrin. Eur J Pharmacol. 2002; 454 1-8
- 78 Wheeler G L, Braden G A, Bray P F et al.. Reduced inhibition by abciximab in platelets with the PlA2 polymorphism. Am Heart J. 2002; 143 76-82
- 79 Weber A A, Jacobs C, Meila D et al.. No evidence for an influence of the human platelet antigen-1 polymorphism on the antiplatelet effects of glycoprotein IIb/IIIa inhibitors. Pharmacogenetics. 2002; 12 581-583
- 80 O'Connor F F, Shields D C, Fitzgerald A et al.. Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes. Blood. 2001; 98 3256-3260
- 81 Walter D H, Schachinger V, Elsner M et al.. Statin therapy is associated with reduced restenosis rates after coronary stent implantation in carriers of the Pl(A2)allele of the platelet glycoprotein IIIa gene. Eur Heart J. 2001; 22 587-595
- 82 Bray P F, Cannon C P, Goldschmidt-Clermont P et al.. The platelet Pl(A2) and angiotensin-converting enzyme (ACE) D allele polymorphisms and the risk of recurrent events after acute myocardial infarction. Am J Cardiol. 2001; 88 347-352
- 83 Borecki I B, Suarez B K. Linkage and association: basic concepts. Adv Genet. 2001; 42 45-66
- 84 Kruglyak L. Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nat Genet. 1999; 22 139-144
- 85 Huttley G A, Smith M W, Carrington M, O'Brien S J. A scan for linkage disequilibrium across the human genome. Genetics. 1999; 152 1711-1722
- 86 Stephens J C, Schneider J A, Tanguay D A et al.. Haplotype variation and linkage disequilibrium in 313 human genes. Science. 2001; 293 489-493
Paul F BrayM.D.
Department of Medicine, Thrombosis Research Section, Baylor College of Medicine
BCM 286, N 1319, Houston, TX 77030
Email: pbray@bcm.tmc.edu