Skip to content
2000
image of The Impact of Single Nucleotide Polymorphisms and Other Mechanisms on Aspirin Resistance

Abstract

Atherosclerosis and ischemic events play a pivotal role in the pathogenesis of several cardiovascular diseases (CVD). The primary aim of preventing recurrent thrombosis in patients who underwent cardiovascular surgery is the antiplatelet agent administration. Nevertheless, despite the aspirin therapy or double (aspirin plus clopidogrel) therapy, the effectiveness of antithrombotic treatment remains controversial. In recent years, we have learned that some percentage of patients still demonstrate no clinical response to aspirin treatment and may experience a vascular complication. This article provides an overview of recent scientific studies that have focused on experimental detection and genotyping of single nucleotide polymorphisms (SNPs) in patients, involving the main therapeutic target genes: cyclooxygenase COX-1 and COX-2, guanylate cyclase GUCY1A3, the glycoprotein complex GPIIb-IIIa, and the platelet receptor protein PEAR1.” The aspirin resistance (AR) ranges considerably from 0% to 66% in patients with ischemic heart disease (IHD) and relatively healthy people (control group). SNP distribution analysis has been proposed to explain the inadequate high platelet reactivity (HPR) among patients with IHD under aspirin treatment. Various SNPs have been proposed to explain the development of CVD and the persistent HPR under aspirin treatment widely used in the prevention of recurrent cardiovascular thrombotic events. Meanwhile, the efficacy of aspirin therapy in secondary thrombosis prevention in patients with IHD is not strongly associated with known SNP. The inconsistent results of different AR clinical trials are likely due to the design of the experiments and methodological and quantitative issues; therefore, careful interpretation of the SNP genotyping results is necessary.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/chddt/10.2174/011871529X361464250319084053
2025-04-04
2025-09-25

  • From This Site

    /content/journals/chddt/10.2174/011871529X361464250319084053
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Montinari M.R. Minelli S. De Caterina R. The first 3500 years of aspirin history from its roots – A concise summary. Vascul. Pharmacol. 2019 113 1 8 10.1016/j.vph.2018.10.008 30391545
    [Google Scholar]
  2. Collaboration A.T. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002 324 7329 71 86 10.1136/bmj.324.7329.71
    [Google Scholar]
  3. Bunimov N. Laneuville O. Antiplatelet therapies: aspirin at the heart of new directions. Cardiovasc. Hematol. Disord. Drug Targ 2014 13 3 173 184 10.2174/1871529X1303140129154040 24479717
    [Google Scholar]
  4. Patrono C. Rocca B. Aspirin, 110 years later. J. Thromb. Haemost. 2009 7 Suppl. 1 258 261 10.1111/j.1538‑7836.2009.03391.x 19630812
    [Google Scholar]
  5. Undas A. Brummel-Ziedins K. Mann K.G. Why does aspirin decrease the risk of venous thromboembolism? On old and novel antithrombotic effects of acetyl salicylic acid. J. Thromb. Haemost. 2014 12 11 1776 1787 10.1111/jth.12728 25213262
    [Google Scholar]
  6. Patrono C. Low-dose aspirin for the prevention of atherosclerotic cardiovascular disease. Eur. Heart J. 2024 45 27 2362 2376 10.1093/eurheartj/ehae324 38839268
    [Google Scholar]
  7. Corazzi T. Leone M. Maucci R. Corazzi L. Gresele P. Direct and irreversible inhibition of cyclooxygenase-1 by nitroaspirin (NCX 4016). J. Pharmacol. Exp. Ther. 2005 315 3 1331 1337 10.1124/jpet.105.089896 16144976
    [Google Scholar]
  8. Goodman T. Ferro A. Sharma P. Pharmacogenetics of aspirin resistance: a comprehensive systematic review. Br. J. Clin. Pharmacol. 2008 66 2 222 232 10.1111/j.1365‑2125.2008.03183.x 18429969
    [Google Scholar]
  9. Frelinger A.L. III Li Y. Linden M.D. Barnard M.R. Fox M.L. Christie D.J. Furman M.I. Michelson A.D. Association of cyclooxygenase-1-dependent and -independent platelet function assays with adverse clinical outcomes in aspirin-treated patients presenting for cardiac catheterization. Circulation 2009 120 25 2586 2596 10.1161/CIRCULATIONAHA.109.900589 19996015
    [Google Scholar]
  10. Johnston S.C. Easton J.D. Farrant M. Barsan W. Conwit R.A. Elm J.J. Kim A.S. Lindblad A.S. Palesch Y.Y. Clinical research collaboration, neurological emergencies treatment trials network, and the POINT investigators. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N. Engl. J. Med. 2018 379 3 215 225 10.1056/NEJMoa1800410 29766750
    [Google Scholar]
  11. Pan Y. Elm J.J. Li H. Easton J.D. Wang Y. Farrant M. Meng X. Kim A.S. Zhao X. Meurer W.J. Liu L. Dietrich D. Wang Y. Johnston S.C. Outcomes associated with clopidogrel-aspirin use in minor stroke or transient ischemic attack: a pooled analysis of clopidogrel in high-risk patients with acute non-disabling cerebrovascular events (CHANCE) and platelet-oriented inhibition in new TIA and mnor ischemic stroke (POINT) trials. JAMA Neurol. 2019 76 12 1466 1473 10.1001/jamaneurol.2019.2531 31424481
    [Google Scholar]
  12. Willems L.H. Maas D.P.M.S.M. Kramers K. Reijnen M.M.P.J. Riksen N.P. Ten Cate H. van der Vijver-Coppen R.J. de Borst G.J. Mees B.M.E. Zeebregts C.J. Hannink G. Warlé M.C. Antithrombotic therapy for symptomatic peripheral arterial disease: a systematic review and network meta-analysis. Drugs 2022 82 12 1287 1302 10.1007/s40265‑022‑01756‑6 35997941
    [Google Scholar]
  13. Coma-Canella I. Velasco A. Variability in individual responsiveness to aspirin: clinical implications and treatment. Cardiovasc. Hematol. Disord. Drug Targ 2007 7 4 274 287 10.2174/187152907782793590 18220726
    [Google Scholar]
  14. Homoródi N. Kovács E.G. Leé S. Katona É. Shemirani A.H. Haramura G. Balogh L. Bereczky Z. Szőke G. Péterfy H. Kiss R.G. Édes I. Muszbek L. The lack of aspirin resistance in patients with coronary artery disease. J. Transl. Med. 2016 14 1 74 10.1186/s12967‑016‑0827‑7 26980433
    [Google Scholar]
  15. Kessler T. Wolf B. Eriksson N. Kofink D. Mahmoodi B.K. Rai H. Tragante V. Åkerblom A. Becker R.C. Bernlochner I. Bopp R. James S. Katus H.A. Mayer K. Munz M. Nordio F. O’Donoghue M.L. Sager H.B. Sibbing D. Solakov L. Storey R.F. Wobst J. Asselbergs F.W. Byrne R.A. Erdmann J. Koenig W. Laugwitz K.L. ten Berg J.M. Wallentin L. Kastrati A. Schunkert H. Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention. Cardiovasc. Res. 2019 115 10 1512 1518 10.1093/cvr/cvz015 30768153
    [Google Scholar]
  16. Papp E. Havasi V. Bene J. Komlosi K. Czopf L. Magyar E. Feher C. Feher G. Horvath B. Marton Z. Alexy T. Habon T. Szabo L. Toth K. Melegh B. Glycoprotein IIIA gene (PlA) polymorphism and aspirin resistance: is there any correlation? Ann. Pharmacother. 2005 39 6 1013 1018 10.1345/aph.1E227 15840736
    [Google Scholar]
  17. Hankey G.J. Eikelboom J.W. Aspirin resistance. Lancet 2006 367 9510 606 617 10.1016/S0140‑6736(06)68040‑9 16488805
    [Google Scholar]
  18. Gladding P.A. Webster M.W.I. Farrell H.B. Zeng I.S.L. Park R. Ruijne N. The antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy volunteers. Am. J. Cardiol. 2008 101 7 1060 1063 10.1016/j.amjcard.2007.11.054 18359332
    [Google Scholar]
  19. Saxena A. Schrör K. Hohlfeld T. High on treatment platelet reactivity against aspirin by non-steroidal anti-inflammatory drugs – pharmacological mechanisms and clinical relevance. Thromb. Haemost. 2013 109 5 825 833 10.1160/TH12‑07‑0532 23238666
    [Google Scholar]
  20. Catella-Lawson F. Reilly M.P. Kapoor S.C. Cucchiara A.J. DeMarco S. Tournier B. Vyas S.N. FitzGerald G.A. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N. Engl. J. Med. 2001 345 25 1809 1817 10.1056/NEJMoa003199 11752357
    [Google Scholar]
  21. 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 17 3 163 169 10.1080/09537100500441101 16702043
    [Google Scholar]
  22. Macchi L. Christiaens L. Brabant S. Sorel N. Allal J. Mauco G. Brizard A. Resistance to aspirin in vitro is associated with increased platelet sensitivity to adenosine diphosphate. Thromb. Res. 2002 107 1-2 45 49 10.1016/S0049‑3848(02)00210‑4 12413588
    [Google Scholar]
  23. Wong S. Appleberg M. Ward C.M. Lewis D.R. Aspirin resistance in cardiovascular disease: a review. Eur. J. Vasc. Endovasc. Surg. 2004 27 5 456 465 10.1016/j.ejvs.2003.12.025 15079767
    [Google Scholar]
  24. Badimon L. Padró T. Vilahur G. Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease. Eur. Heart J. Acute Cardiovasc. Care 2012 1 1 60 74 10.1177/2048872612441582 24062891
    [Google Scholar]
  25. Khan H. Kanny O. Syed M.H. Qadura M. Aspirin resistance in vascular disease: a review highlighting the critical need for improved point-of-care testing and personalized therapy. Int. J. Mol. Sci. 2016 23 19 11317 10.3390/ijms231911317 36232618
    [Google Scholar]
  26. Syed F.A. Bett J.H.N. Walters D.L. Anti-platelet therapy for acute coronary syndrome: a review of currently available agents and what the future holds. Cardiovasc. Hematol. Disord. Drug Targ 2011 11 2 79 86 10.2174/187152911798347007 22044036
    [Google Scholar]
  27. Pedersen A.K. FitzGerald G.A. Dose-related kinetics of aspirin. Presystemic acetylation of platelet cyclooxygenase. N. Engl. J. Med. 1984 311 19 1206 1211 10.1056/NEJM198411083111902 6436696
    [Google Scholar]
  28. Gonzalez-Conejero R. Rivera J. Corral J. Acuña C. Guerrero J.A. Vicente V. Biological assessment of aspirin efficacy on healthy individuals: heterogeneous response or aspirin failure? Stroke 2005 36 2 276 280 10.1161/01.STR.0000151362.65339.f9 15604423
    [Google Scholar]
  29. Myers R.A. Ortel T.L. Waldrop A. Dave S. Ginsburg G.S. Voora D. Aspirin effects on platelet gene expression are associated with a paradoxical, increase in platelet function. Br. J. Clin. Pharmacol. 2022 88 5 2074 2083 10.1111/bcp.15127 34705291
    [Google Scholar]
  30. Hobikoglu G.F. Norgaz T. Aksu H. Ozer O. Erturk M. Nurkalem Z. Narin A. High frequency of aspirine resistance in patients with acute coronary syndrome. Tohoku J. Exp. Med. 2005 207 1 59 64 10.1620/tjem.207.59
    [Google Scholar]
  31. Wang B.Y. Tan S.J. Platelet glycoprotein IIIa gene polymorphism (Leu33Pro) and aspirin resistance in a very elderly Chinese population. Genet. Test. Mol. Biomarkers 2014 18 6 389 393 10.1089/gtmb.2013.0433 24720773
    [Google Scholar]
  32. Grosser T. Fries S. Lawson J.A. Kapoor S.C. Grant G.R. FitzGerald G.A. Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin. Circulation 2013 127 3 377 385 10.1161/CIRCULATIONAHA.112.117283 23212718
    [Google Scholar]
  33. Mueller M.R. Salat A. Stangl P. Murabito M. Pulaki S. Boehm D. Koppensteiner R. Ergun E. Mittlboeck M. Schreiner W. Losert U. Wolner E. Variable platelet response to low-dose ASA and the risk of limb deterioration in patients submitted to peripheral arterial angioplasty. Thromb. Haemost. 1997 78 3 1003 1007 10.1055/s‑0038‑1657677 9308744
    [Google Scholar]
  34. Macchi L. Christiaens L. Brabant S. Sorel N. Ragot S. Allal J. Mauco G. Brizard A. 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 Ibα) polymorphisms. J. Am. Coll. Cardiol. 2003 42 6 1115 1119 10.1016/S0735‑1097(03)00921‑5 13678940
    [Google Scholar]
  35. Abderrazek F. Chakroun T. Addad F. Dridi Z. Gerotziafas G. Gamra H. Hassine M. Elalamy I. The GPIIIa PlA polymorphism and the platelet hyperactivity in Tunisian patients with stable coronary artery disease treated with aspirin. Thromb. Res. 2010 125 6 e265 e268 10.1016/j.thromres.2010.01.011 20138334
    [Google Scholar]
  36. Halushka M.K. Walker L.P. Halushka P.V. Genetic variation in cyclooxygenase 1: Effects on response to aspirin. Clin. Pharmacol. Ther. 2003 73 1 122 130 10.1067/mcp.2003.1 12545150
    [Google Scholar]
  37. Muir A.R. McMullin M.F. Patterson C. McKeown P.P. Assessment of aspirin resistance varies on a temporal basis in patients with ischaemic heart disease. Heart 2009 95 15 1225 1229 10.1136/hrt.2008.150631 18697805
    [Google Scholar]
  38. Mikkelsson J. Reséndiz J. Viiri L. Backman J. Kankuri E. Karhunen P. Lassila R. Lepäntalo A. Polymorphisms of COX-1 and GP VI associate with the antiplatelet effect of aspirin in coronary artery disease patients. Thromb. Haemost. 2006 95 2 253 259 10.1160/TH05‑07‑0516 16493486
    [Google Scholar]
  39. Kessler T. Vilne B. Schunkert H. The impact of genome‐wide association studies on the pathophysiology and therapy of cardiovascular disease. EMBO Mol. Med. 2016 8 7 688 701 10.15252/emmm.201506174 27189168
    [Google Scholar]
  40. Erdmann J. Kessler T. Munoz Venegas L. Schunkert H. A decade of genome-wide association studies for coronary artery disease: the challenges ahead. Cardiovasc. Res. 2018 114 9 1241 1257 10.1093/cvr/cvy084 29617720
    [Google Scholar]
  41. Schunkert H. von Scheidt M. Kessler T. Stiller B. Zeng L. Vilne B. Genetics of coronary artery disease in the light of genome-wide association studies. Clin. Res. Cardiol. 2018 107 S2 Suppl. 2 2 9 10.1007/s00392‑018‑1324‑1 30022276
    [Google Scholar]
  42. Glicksberg B.S. Amadori L. Akers N.K. Sukhavasi K. Franzén O. Li L. Belbin G.M. Akers K.L. Shameer K. Badgeley M.A. Johnson K.W. Readhead B. Darrow B.J. Kenny E.E. Betsholtz C. Ermel R. Skogsberg J. Ruusalepp A. Schadt E.E. Dudley J.T. Ren H. Kovacic J.C. Giannarelli C. Li S.D. Björkegren J.L.M. Chen R. Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits. BMC Med. Genomics 2019 12 S6 Suppl. 6 108 10.1186/s12920‑019‑0542‑3 31345219
    [Google Scholar]
  43. Deloukas P. Kanoni S. Deloukas P. Kanoni S. Willenborg C. Farrall M. Assimes T.L. Thompson J.R. Ingelsson E. Saleheen D. Erdmann J. Goldstein B.A. Stirrups K. König I.R. Cazier J-B. Johansson Å. Hall A.S. Lee J-Y. Willer C.J. Chambers J.C. Esko T. Folkersen L. Goel A. Grundberg E. Havulinna A.S. Ho W.K. Hopewell J.C. Eriksson N. Kleber M.E. Kristiansson K. Lundmark P. Lyytikäinen L-P. Rafelt S. Shungin D. Strawbridge R.J. Thorleifsson G. Tikkanen E. Zuydam N.Van Voight, B.F.; Waite, L.L.; Zhang, W.; Ziegler, A.; Absher, D.; Altshuler, D.; Balmforth, A.J.; Barroso, I.; Braund, P.S.; Burgdorf, C.; Boehm, S.Claudi.; Cox, D.; Dimitriou, M.; Do, R.; Consortium, D.; Consortium, C.; Doney, A.S.F.; Mokhtari, N.El.; Eriksson, P.; Fischer, K.; Fontanillas, P.; Cereceda, A.Franco.; Gigante, B.; Groop, L.; Gustafsson, S.; Hager, J.; Hallmans, G.; Han, B.-G.; Hunt, S.E.; Kang, H.M.; Illig, T.; Kessler, T.; Knowles, J.W.; Kolovou, G.; Kuusisto, J.; Langenberg, C.; Langford, C.; Leander, K.; Lokki, M.-L.; Lundmark, A.; McCarthy, M.I.; Meisinger, C.; Melander, O.; Mihailov, E.; Maouche, S.; Morris, A.D.; Nurasyid, M.Müller.; Consortium, M.; Nikus, K.; Peden, J.F.; Rayner, N.; Rasheed, A.; Rosinger, S.; Rubin, D.; Rumpf, M.P.; Schäfer, A.; Sivananthan, M.; Song, C.; Stewart, A.F.R.; Tan, S.-T.; Thorgeirsson, G.; Schoot, C.V.D.; Wagner, P.J.; Consortium, W.T.; Wells, G.A.; Wild, P.S.; Yang, T.-P.; Amouyel, P.; Arveiler, D.; Basart, H.; Boehnke, M.; Boerwinkle, E.; Brambilla, P.; Cambien, F.; Cupples, A.L.; Faire, U.de.; Dehghan, A.; Diemert, P.; Epstein, S.E.; Evans, A.; Ferrario, M.M.; Ferrières, J.; Gauguier, D.; Go, A.S.; Goodall, A.H.; Gudnason, V.; Hazen, S.L.; Holm, H.; Iribarren, C.; Jang, Y.; Kähönen, M.; Kee, F.; Kim, H.-S.; Klopp, N.; Koenig, W.; Kratzer, W.; Kuulasmaa, K.; Laakso, M.; Laaksonen, R.; Lee, J.-Y.; Lind, L.; Ouwehand, W.H.; Parish, S.; Park, J.E.; Pedersen, N.L.; Peters, A.; Quertermous, T.; Rader, D.J.; Salomaa, V.; Schadt, E.; Shah, S.H.; Sinisalo, J.; Stark, K.; Stefansson, K.; Trégouët, D.-A.; Virtamo, J.; Wallentin, L.; Wareham, N.; Zimmermann, M.E.; Nieminen, M.S.; Hengstenberg, C.; Sandhu, M.S.; Pastinen, T.; Syvänen, A.-C.; Hovingh, G.; Dedoussis, G.; Franks, P.W.; Lehtimäki, T.; Metspalu, A.; Zalloua, P.A.; Siegbahn, A.; Schreiber, S.; Ripatti, S.; Blankenberg, S.S.; Perola, M.; Clarke, R.; Boehm, B.O.; Donnell, C.O; Reilly, M.P.; März, W.; Collins, R.; Kathiresan, S.; Hamsten, A.; Kooner, J.S.; Thorsteinsdottir, U.; Danesh, J.; Palmer, C.N.A.; Roberts, R.; Watkins, H.; Schunkert, H.; Samani, N.J. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat. Genet. 2013 45 25 33 10.1038/ng.2480
    [Google Scholar]
  44. Faraday N. Yanek L.R. Mathias R. Herrera-Galeano J.E. Vaidya D. Moy T.F. Fallin M.D. Wilson A.F. Bray P.F. Becker L.C. Becker D.M. Heritability of platelet responsiveness to aspirin in activation pathways directly and indirectly related to cyclooxygenase-1. Circulation 2007 115 19 2490 2496 10.1161/CIRCULATIONAHA.106.667584 17470694
    [Google Scholar]
  45. Vane J.R. Bakhle Y.S. Botting R.M. Cyclooxygenases 1 and 2. Annu. Rev. Pharmacol. Toxicol. 1998 38 1 97 120 10.1146/annurev.pharmtox.38.1.97 9597150
    [Google Scholar]
  46. Tang E.H.C. Vanhoutte P.M. Gene expression changes of prostanoid synthases in endothelial cells and prostanoid receptors in vascular smooth muscle cells caused by aging and hypertension. Physiol. Genomics 2008 32 3 409 418 10.1152/physiolgenomics.00136.2007 18056786
    [Google Scholar]
  47. Lushnikova E.L. Nepomnyashchikh L.M. Pichigin V.I. Klinnikova M.G. Nepomnyashchikh R.D. Sergeevichev D.S. Expression of mRNA of apolipoprotein E, apolipoprotein A-IV, and matricellular proteins in the myocardium and intensity of fibroplastic processes during experimental hypercholesterolemia. Bull. Exp. Biol. Med. 2013 156 2 271 275 10.1007/s10517‑013‑2328‑5 24319766
    [Google Scholar]
  48. Smith W.L. Garavito R.M. DeWitt D.L. Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J. Biol. Chem. 1996 271 52 33157 33160 10.1074/jbc.271.52.33157 8969167
    [Google Scholar]
  49. Severino P. D’Amato A. Pucci M. Infusino F. Adamo F. Birtolo L.I. Netti L. Montefusco G. Chimenti C. Lavalle C. Maestrini V. Mancone M. Chilian W.M. Fedele F. Ischemic heart disease pathophysiology paradigms overview: from plaque activation to microvascular dysfunction. Int. J. Mol. Sci. 2020 21 21 8118 10.3390/ijms21218118 33143256
    [Google Scholar]
  50. Karim S. Habib A. Lévy-Toledano S. Maclouf J. Cyclooxygenase-1 and -2 of endothelial cells utilize exogenous or endogenous arachidonic acid for transcellular production of thromboxane. J. Biol. Chem. 1996 271 20 12042 12048 10.1074/jbc.271.20.12042 8662657
    [Google Scholar]
  51. Sharma V. Kaul S. Al-Hazzani A. Alshatwi A.A. Jyothy A. Munshi A. Association of COX-2 rs20417 with aspirin resistance. J. Thromb. Thrombolysis 2013 35 1 95 99 10.1007/s11239‑012‑0777‑8 22763923
    [Google Scholar]
  52. Russwurm M. Koesling D. Isoforms of NO-sensitive guanylyl cyclase. Mol. Cell. Biochem. 2002 230 1/2 159 164 10.1023/A:1014252309493 11952091
    [Google Scholar]
  53. Vanhoutte P.M. Shimokawa H. Feletou M. Tang E.H.C. Endothelial dysfunction and vascular disease - a 30th anniversary update. Acta Physiol. (Oxf.) 2017 219 1 22 96 10.1111/apha.12646 26706498
    [Google Scholar]
  54. Li J-L Liu L-Y Jiang D-D Jiang Y-Y Zhou G-Q Mo D-C. Luo M Association between GUCY1A3 genetic polymorphism and large artery atherosclerotic stroke risk in Chinese Han population: a case control study. Lipids Health Dis. 2019 18 1 233 10.1186/s12944‑019‑1177‑2 31883534
    [Google Scholar]
  55. Grześk G. Witczyńska A. Węglarz M. Wołowiec Ł. Nowaczyk J. Grześk E. Nowaczyk A. Soluble guanylyl cyclase activators-promising therapeutic option in the pharmacotherapy of heart failure and pulmonary hypertension. Molecules 2023 28 2 861 10.3390/molecules28020861 36677920
    [Google Scholar]
  56. Ehret G.B. Munroe P.B. Rice K.M. Bochud M. Johnson A.D. Chasman D.I. Smith A.V. Tobin M.D. Verwoert G.C. Hwang S-J. Pihur V. Vollenweider P. O’Reilly P.F. Amin N. Bragg-Gresham J.L. Teumer A. Glazer N.L. Launer L. Zhao J.H. Aulchenko Y. Heath S. Sõber S. Parsa A. An-Luan J. Arora P. Dehghan A. Zhang F. Lucas G. Hicks A.A. Jackson A.U. Peden J.F. Tanaka T. Wild S.H. Rudan I. Igl W. Milaneschi Y. Parker A.N. Fava C. Chambers J.C. Fox E.R. Kumari M. Go M.J. Harst P.V.D. Kao W.H.L. Sjögren M. Vinay D. Alexander M. Tabara Y. Shaw-Hawkins S. Whincup P.H. Liu Y. Shi G. Kuusisto J. Tayo B. Seielstad M. Sim X. Nguyen K-D.H. Lehtimäki T. Matullo G. Wu Y. Gaunt T.R. Onland-Moret N. Cooper M.N. Platou C.G.P. Org E. Hardy R. Dahgam S. Palmen J. Vitart V. Braund P.S. Kuznetsova T. Uiterwaal C.S.P.M. Adeyemo A. Palmas W. Campbell H. Ludwig B. Tomaszewski M. Tzoulaki I. Palmer N.D. Garcia M. Chang Y-P.C. O’ Connell J.R. Steinle N.I. Grobbee D.E. Arking D.E. Kardia S.L. Morrison A.C. Hernandez D. Najjar S. McArdle W.L. Hadley D. Brown M.J. Connell J.M. Hingorani A.D. Day I.N.M. Lawlor D.A. Beilby J.P. Lawrence R.W. Clarke R. Hopewell J.C. Ongen H. Dreisbach A.W. Li Y. Young J. Bis J.C. Kähönen M. Viikari J. Adair L.S. Lee N.R. Chen M-H. Olden M. Pattaro C. Bolton J.A.H. Köttgen A. Bergmann S. Mooser V. Chaturvedi N. Frayling T.M. Islam M. Jafar T.H. Erdmann J. Kulkarni S.R. Bornstein S.R. Grässler J. Groop L. Voight B.F. Kettunen J. Howard P. Taylor A. Guarrera S. Ricceri F. Emilsson V. Plump A. Barroso I. Khaw K-T. Weder A.B. Hunt S.C. Sun Y.V. Bergman R.N. Collins F.S. Bonnycastle L.L. Scott L.J. Stringham H.M. Peltonen L. Perola M. Vartiainen E. Brand S-M. Staessen J.A. Wang T.J. Burton P.R. Artigas M.S. Dong Y. Snieder H. Wang X. Zhu H. Lohman K.K. Rudock M.E. Heckbert S.R. Smith N.L. Wiggins K.L. Doumatey A. Shriner D. Veldre G. Viigimaa M. Kinra S. Prabhakaran D. Tripathy V. Langefeld C.D. Rosengren A. Thelle D.S. Corsi A.M. Singleton A. Forrester T. Hilton G. McKenzie C.A. Salako T. Iwai N. Kita Y. Ogihara T. Ohkubo T. Okamura T. Ueshima H. Umemura S. Eyheramendy S. Meitinger T. Wichmann H. Cho Y. Shin.; Kim, H.-L.; Lee, J.-Y.; Scott, J.; Sehmi, J.S.; Zhang, W.; Hedblad, B.; Nilsson, P.; Smith, G.Davey.; Wong, A.; Narisu, N.; Stančáková, A.; Raffel, L.J.; Yao, J.; Kathiresan, S.; Donnell, C.J O; Schwartz, S.M.; Ikram, M.; Jr, W.L.; Mosley, T.H.; Seshadri, S.; Shrine, N.R G.; Wain, L.V.; Morken, M.A.; Swift, A.J.; Laitinen, J.; Prokopenko, I.; Zitting, P.; Cooper, J.A.; Humphries, S.E.; Danesh, J.; Rasheed, A.; Goel, A.; Hamsten, A.; Watkins, H.; Bakker, S.J L.; Gilst, W.H.V.; Janipalli, C.S.; Mani, K.; Yajnik, C.S.; Hofman, A.; Mattace-Raso, F.U S; Oostra, B.A.; Demirkan, A.; Isaacs, A.; Rivadeneira, F.; Lakatta, E.G.; Orru, M.; Scuteri, A.; Ala-Korpela, M.; Kangas, A.J.; Lyytikäinen, L.-P.; Soininen, P.; Tukiainen, T.; Würtz, P.; Ong, R.T.-H.; Dörr, M.; Kroemer, H.K.; Völker, U.; Völzke, H.; Galan, P.; Hercberg, S.; Lathrop, M.; Zelenika, D.; Deloukas, P.; Mangino, M.; Spector, T.D.; Zhai, G.; Meschia, J.F.; Nalls, M.A.; Sharma, P.; Terzic, J.; Kumar, M.Kranthi.; Denniff, M.; Zukowska-Szczechowska, E.; Wagenknecht, L.E.; Fowkes, F.R.; Charchar, F.J.; Schwarz, P.E.H.; Hayward, C.; Guo, X.; Rotimi, C.; Bots, M.L.; Brand, E.; Samani, N.J.; Polasek, O.; Talmud, P.J.; Nyberg, F.; Kuh, D.; Laan, M.; Hveem, K.; Palmer, L.J.; Schouw, Y.T.V.D.; Casas, J.P.; Mohlke, K.L.; Vineis, P.; Raitakari, O.; Ganesh, S.K.; Wong, T.Y.; Tai, E.; Cooper, R.S.; Laakso, M.; Rao, D.C.; Harris, T.B.; Morris, R.W.; Dominiczak, A.F.; Kivimaki, M.; Marmot, M.G.; Miki, T.; Saleheen, D.; Chandak, G.R.; Coresh, J.; Navis, G.; Salomaa, V.; Han, B.-G.; Zhu, X.; Kooner, J.S.; Melander, O.; Ridker, P.M.; Bandinelli, S.; Gyllensten, U.B.; Wright, A.F.; Wilson, J.F.; Ferrucci, L.; Farrall, M.; Tuomilehto, J.; Pramstaller, P.P.; Elosua, R.; Soranzo, N.; Sijbrands, E.J.G.; Altshuler, D.; Loos, R.J.F.; Shuldiner, A.R.; Gieger, C.; Meneton, P.; Uitterlinden, A.G.; Wareham, N.J.; Gudnason, V.; Rotter, J.I.; Rettig, R.; Uda, M.; Strachan, D.P.; Witteman, J.C M.; Hartikainen, A.-L.; Beckmann, J.S.; Boerwinkle, E.; Vasan, R.S.; Boehnke, M.; Larson, M.G.; Järvelin, M.-R.; Psaty, B.M.; Abecasis, G.R.; Chakravarti, A.; Elliott, P.; Duijn, C.M.V.; Newton-Cheh, C.; Levy, D.; Caulfield, M.J.; Johnson, T. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 2012 478 7367 103 109 10.1038/nature10405 21909115
    [Google Scholar]
  57. Guo Y. Garcia-Barrio M.T. Wang L. Chen Y.E. Experimental biology for the identification of casual pathways in atherosclerosis. Cardiovasc. Drugs Ther. 2016 30 1 1 11 10.1007/s10557‑016‑6644‑7 26847647
    [Google Scholar]
  58. Hall K.T. Kessler T. Buring J.E. Passow D. Sesso H.D. Zee R.Y.L. Ridker P.M. Chasman D.I. Schunkert H. Genetic variation at the coronary artery disease risk locus GUCY1A3 modifies cardiovascular disease prevention effects of aspirin. Eur. Heart J. 2019 40 41 3385 3392 10.1093/eurheartj/ehz384 31228190
    [Google Scholar]
  59. Friebe A. Englert N. NO-sensitive guanylyl cyclase in the lung. Br. J. Pharmacol. 2020 179 11 2328 2343 10.1111/bph.15345 33332689
    [Google Scholar]
  60. Alexander J.H. Harrington R.A. Tuttle R.H. Berdan L.G. Lincoff A.M. Deckers J.W. Simoons M.L. Guerci A. Hochman J.S. Wilcox R.G. Kitt M.M. Eisenberg P.R. Califf R.M. Topol E.J. Karsh K. Ruzyllo W. Stepinska J. Widimsky P. Boland J.B. Armstrong P.W. Prior aspirin use predicts worse outcomes in patients with non-ST-elevation acute coronary syndromes. PURSUIT Investigators. Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy. Am. J. Cardiol. 1999 83 8 1147 1151 10.1016/S0002‑9149(99)00049‑1 10215274
    [Google Scholar]
  61. Galley J.C. Miller M.P. Sanker S. Liu M. Sharina I. Martin E. Gomez D. Straub A.C. FoxO4 controls sGCβ transcription in vascular smooth muscle. Am. J. Physiol. Heart Circ. Physiol. 2022 322 3 H417 H426 10.1152/ajpheart.00551.2021 35089807
    [Google Scholar]
  62. Satoh T. Wang L. Espinosa-Dies C. Wang B. Hahn S.A. Noda K. Rochon E.R. Dent M.R. Levine A.R. Baust J.J. Wyman S. Wu Y.L. Triantafyllou G.A. Tang Y. Reynolds M. Shiva S. St. Hilaire C. Gomez D. Goncharov D.A. Goncharova E.A. Chan S.Y. Straub A.C. Lai Y-C. McTiernan C.F. Gladwin M.T. Metabolic syndrome mediates ROS-miR-193b-NFYA-dependent down regulation of sGC and contributes to exercise-induced pulmonary hypertension in heart failure with preserved ejection fraction. Circulation 2021 144 8 615 637 10.1161/CIRCULATIONAHA.121.053889 34157861
    [Google Scholar]
  63. Cong N.V. Uzan G. Gross M.S. Jegou-Foubert C. Frachet P. Boucheix C. Marguerie G. Frézal J. Assignment of human platelet GP2B (GPIIb) gene to chromosome 17, region q21.1-q21.3. Hum. Genet. 1988 80 4 389 392 10.1007/BF00273658 3198118
    [Google Scholar]
  64. Meisel C. López J.A. Stangl K. Role of platelet glycoprotein polymorphisms in cardiovascular diseases. Naunyn Schmied Arch. Pharmacol. 2004 369 1 38 54 10.1007/s00210‑003‑0828‑y 14614592
    [Google Scholar]
  65. Tsysar Y.V. Andriiets O.A. Dubyk L.V. Dyak K.V. Radu R.M. Genetic screening of PLA1/PLA2 polymorphous marker of integrin beta 3 (ITGB3) GP IIIa gene in adolescent girls with puberty menorrhagia. J. Med. Life 2023 16 2 261 266 10.25122/jml‑2022‑0350 36937472
    [Google Scholar]
  66. Lozano M.L. Cook A. Bastida J.M. Paul D.S. Iruin G. Cid A.R. Adan-Pedroso R. Ramón González-Porras J. Hernández-Rivas J.M. Fletcher S.J. Johnson B. Morgan N. Ferrer-Marin F. Vicente V. Sondek J. Watson S.P. Bergmeier W. Rivera J. Novel mutations in RASGRP2, which encodes CalDAG-GEFI, abrogate Rap1 activation, causing platelet dysfunction. Blood 2016 128 9 1282 1289 10.1182/blood‑2015‑11‑683102 27235135
    [Google Scholar]
  67. Botero J.P. Lee K. Branchford B.R. Bray P.F. Freson K. Lambert M.P. Luo M. Mohan S. Ross J.E. Bergmeier W. Di Paola J. Glanzmann thrombasthenia: genetic basis and clinical correlates. Haematologica 2020 105 4 888 894 10.3324/haematol.2018.214239 32139434
    [Google Scholar]
  68. Nurden A.T. Glanzmann thrombasthenia. Orphanet J. Rare Dis. 2006 1 1 10 10.1186/1750‑1172‑1‑10 16722529
    [Google Scholar]
  69. Bledzka K. Smyth S.S. Plow E.F. Integrin αIIbβ3. Circ. Res. 2013 112 8 1189 1200 10.1161/CIRCRESAHA.112.300570 23580774
    [Google Scholar]
  70. Mitchell W.B. Li J. French D.L. Coller B.S. αIIbβ3 biogenesis is controlled by engagement of αIIb in the calnexin cycle via the N15-linked glycan. Blood 2006 107 7 2713 2719 10.1182/blood‑2005‑07‑2990 16304048
    [Google Scholar]
  71. Chen C.H. Lo Y.K. Ke D. Liu C.K. Liou C.W. Wu H.L. Lai M.L. Platelet glycoprotein Ia C807T, Ib C3550T, and IIIa PlA1/A2 polymorphisms and ischemic stroke in young Taiwanese. J. Neurol. Sci. 2004 227 1 1 5 10.1016/j.jns.2004.07.019 15546585
    [Google Scholar]
  72. Slowik A. Dziedzic T. Turaj W. Pera J. Glodzik-Sobanska L. Szermer P. Malecki M.T. Figlewicz D.A. Szczudlik A. A2 alelle of GpIIIa gene is a risk factor for stroke caused by large-vessel disease in males. Stroke 2004 35 7 1589 1593 10.1161/01.STR.0000132194.24663.3d 15178823
    [Google Scholar]
  73. Weiss E.J. Bray P.F. Tayback M. Schulman S.P. Kickler T.S. Becker L.C. Weiss J.L. Gerstenblith G. Goldschmidt-Clermont P.J. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N. Engl. J. Med. 1996 334 17 1090 1094 10.1056/NEJM199604253341703 8598867
    [Google Scholar]
  74. Herrera-Galeano J.E. Becker D.M. Wilson A.F. Yanek L.R. Bray P. Vaidya D. Faraday N. Becker L.C. A novel variant in the platelet endothelial aggregation receptor-1 gene is associated with increased platelet aggregability. Arterioscler. Thromb. Vasc. Biol. 2008 28 8 1484 1490 10.1161/ATVBAHA.108.168971 18511696
    [Google Scholar]
  75. Faraday N. Yanek L.R. Yang X.P. Mathias R. Herrera-Galeano J.E. Suktitipat B. Qayyum R. Johnson A.D. Chen M.H. Tofler G.H. Ruczinski I. Friedman A.D. Gylfason A. Thorsteinsdottir U. Bray P.F. O’Donnell C.J. Becker D.M. Becker L.C. Identification of a specific intronic PEAR1 gene variant associated with greater platelet aggregability and protein expression. Blood 2011 118 12 3367 3375 10.1182/blood‑2010‑11‑320788 21791418
    [Google Scholar]
  76. Fisch A.S. Yerges-Armstrong L.M. Backman J.D. Wang H. Donnelly P. Ryan K.A. Parihar A. Pavlovich M.A. Mitchell B.D. O’Connell J.R. Herzog W. Harman C.R. Wren J.D. Lewis J.P. Genetic variation in the platelet endothelial aggregation receptor 1 gene results in endothelial dysfunction. PLoS One 2015 10 9 e0138795 10.1371/journal.pone.0138795 26406321
    [Google Scholar]
  77. Xiang Q. Zhou S. Lewis J.P. Shuldiner A.R. Ren G. Cui Y. Genetic variants of PEAR1 are associated with platelet function and antiplatelet drug efficacy: a systematic review and meta-analysis. Curr. Pharm. Des. 2018 23 44 6815 6827 10.2174/1381612823666170817122043 28820077
    [Google Scholar]
  78. Ansari N. Najafi S. Shahrabi S. Saki N. PEAR1 polymorphisms as a prognostic factor in hemostasis and cardiovascular diseases. J. Thromb. Thromboly 2021 51 1 89 95 10.1007/s11239‑020‑02149‑w 32445063
    [Google Scholar]
  79. Zhang X. Li S. Zhao Y. Tang N. Jia T. Zhou P. Liu J. Shi L. Lu C.Y. Nie X. Genetic variants of PEAR1 and ischemic clinical outcomes in coronary artery disease patients: a systematic review and meta-analysis. Pharmacogenomics 2021 22 10 641 648 10.2217/pgs‑2021‑0022 34075782
    [Google Scholar]
  80. Lewis J.P. Ryan K. O’Connell J.R. Horenstein R.B. Damcott C.M. Gibson Q. Pollin T.I. Mitchell B.D. Beitelshees A.L. Pakzy R. Tanner K. Parsa A. Tantry U.S. Bliden K.P. Post W.S. Faraday N. Herzog W. Gong Y. Pepine C.J. Johnson J.A. Gurbel P.A. Shuldiner A.R. Genetic variation in PEAR1 is associated with platelet aggregation and cardiovascular outcomes. Circ. Cardiovasc. Genet. 2013 6 2 184 192 10.1161/CIRCGENETICS.111.964627 23392654
    [Google Scholar]
  81. Helgason C.M. Bolin K.M. Hoff J.A. Winkler S.R. Mangat A. Tortorice K.L. Brace L.D. Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994 25 12 2331 2336 10.1161/01.STR.25.12.2331 7974569
    [Google Scholar]
  82. Evsyukova H.V. The role of melatonin in pathogenesis of aspirin‐sensitive asthma. Eur. J. Clin. Invest. 1999 29 6 563 567 10.1046/j.1365‑2362.1999.00479.x 10354220
    [Google Scholar]
  83. De Weck A.L. Sanz M.L. Gamboa P.M. Aberer W. Blanca M. Correia S. Erdman S. Jermann J.M. Kanny G. Kowalski M. Mayorga L. Medrala W. Merk A. Sturm G.J. Sainte-Laudy J. Schneider M.S. Sczczeklik A. Weber J.M. Wedi A. Nonsteroidal anti-inflammatory drug hypersensitivity syndrome. A multicenter study. I. Clinical findings and in vitro diagnosis. J. Investig. Allergol. Clin. Immunol. 2009 19 5 355 369 19862935
    [Google Scholar]
  84. Kowalski M.L. Makowska J.S. Blanca M. Bavbek S. Bochenek G. Bousquet J. Bousquet P. Celik G. Demoly P. Gomes E.R. Niżankowska-Mogilnicka E. Romano A. Sanchez-Borges M. Sanz M. Torres M.J. De Weck A. Szczeklik A. Brockow K. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA# and GA2LEN/HANNA. Allergy 2011 66 7 818 829 10.1111/j.1398‑9995.2011.02557.x 21631520
    [Google Scholar]
  85. Demir S. Olgac M. Unal D. Gelincik A. Colakoglu B. Buyukozturk S. Evaluation of hypersensitivity reactions to nonsteroidal anti-inflammatory drugs according to the latest classification. Allergy 2015 70 11 1461 1467 10.1111/all.12689 26173603
    [Google Scholar]
/content/journals/chddt/10.2174/011871529X361464250319084053
Loading
The Impact of Single Nucleotide Polymorphisms and Other Mechanisms on Aspirin Resistance
Bentham Science Publishers ; https://doi.org/10.2174/011871529X361464250319084053
/content/journals/chddt/10.2174/011871529X361464250319084053
/content/journals/chddt/10.2174/011871529X361464250319084053
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: Ischemic heart disease ; thrombosis ; pharmacogenetics ; single nucleotide polymorphisms ; acetylsalicylic acid

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test