Preview

Rational Pharmacotherapy in Cardiology

Advanced search

Study of the Association of V640L (rs6133) Polymorphism in the Platelet P-selectin Gene with Acetylsalicylic Acid Resistance in Patients after Coronary Bypass Surgery

https://doi.org/10.20996/1819-6446-2019-15-3-343-348

Full Text:

Abstract

Aim. To study the association of V640L (rs6133) polymorphism in the P-selectin gene with acetylsalicylic acid (ASA) resistance in patients with coronary heart disease after coronary bypass surgery (CABG).
Material and methods. The study included 104 patients aged 36-78 years (mean age 61.6±6.9 years) with stable angina pectoris: 61 (58.7%) patients had functional class II (according to Canadian Cardiovascular Society), 41 (39.4%) – class III and 2 (1.9%) – class IV. Atherosclerotic lesions of the coronary arteries were confirmed by coronary angiography. The antiplatelet therapy was stopped for at least 5 days before CABG. In the postoperative period, from the first day, all patients received 100 mg of ASA in enteric form, 61 patients received alone ASA therapy, 43 patients – combined antiplatelet therapy: ASA+clopidogrel (75 mg/day). The aggregation study was performed with an optical aggregometer, using 5 μM adenosinediphosphate (ADP) and 1 mM arachidonic acid inductors before CABG, on 1-3 day and on 8-10 day after surgical treatment. DNA samples were examined for the V640L (rs6133) polymorphism in the P-selectin gene by real-time polymerase chain reaction (PCR) using the allele-specific primers.

Results. The frequency of the homozygous GG genotype of the rs6133 polymorphism was 84.6%; heterozygous GT genotype – 15.4%. The amplitude of aggregation with ADP before CABG, on 1-3 day and on 8-10 day after CABG for carriers of homozygotes of allele G vs carriers of the allele T were: 47.9±19.3%, 44.5±17.8%, 30.1±13.2% vs 47.9±17.1%, 46.3±16.5%, 39.6±22.0%, respectively (p=0.497, 0.441 and 0.687, respectively). The amplitude of aggregation with arachidonic acid before CABG, on 1-3 day and on 8-10 day after CABG for carriers of homozygotes
of allele G vs carriers of the allele T, were: 47.9±23.2%, 24.5±21.7%, 12.3±16.3% vs 54.3±17.8%, 29.7±23.7%,  11±10.9%, respectively (p=0.416, 0.825 and 0.872, respectively). In the first 10 days of the postoperative period, 6 thrombotic events (5.7%) were observed in the study group: 2 strokes and 4 perioperative myocardial infarctions. Five events occurred in the group of patients with the GG genotype, 1 event in the group of patients with the GT genotype.
Conclusion. V640L (rs6133) polymorphism in the P-selectin gene is not associated with ASA resistance in patients with coronary artery disease after CABG. The T allele of the rs6133 polymorphism is not associated with increased platelet aggregation activity after CABG and does not increase the risk of adverse events in the first 10 days after CABG.

About the Authors

A. A. Kosinova
Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky
Russian Federation

MD, PhD, Assistant, Chair of Therapy

Partizana Zheleznyaka ul. 1, Krasnoyarsk, 660022 Russia

 



T. S. Mongush
Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky Federal Center for Cardiovascular Surgery
Russian Federation

MD, Doctoral Student, Chair of Therapy; Cardiologist

Partizana Zheleznyaka ul. 1, Krasnoyarsk, 660022 Russia

 Karaulnaya ul. 45, Krasnoyarsk, 660020 Russia



M. D. Goncharov
Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky Federal Center for Cardiovascular Surgery
Russian Federation

MD, Doctoral Student, Chair of Therapy; Laboratory Diagnosis Doctor

Partizana Zheleznyaka ul. 1, Krasnoyarsk, 660022 Russia

Karaulnaya ul. 45, Krasnoyarsk, 660020 Russia



T. N. Subbotina
Siberian Federal University
Russian Federation

MD, PhD (Biology), Head of the Scientific and Practical Laboratory of Molecular Genetic Research Methods

Svobodny prosp. 79, Krasnoyarsk, 660041 Russia



K. S. Semashchenko
Siberian Federal University
Russian Federation

3rd Year Undergraduate Student, Institute of Fundamental Biology and Biotechnology

Svobodny prosp. 79, Krasnoyarsk, 660041 Russia



G. Y. Kochmareva
Siberian Federal University
Russian Federation

2rd Year Master Student, Institute of Fundamental Biology and Biotechnology

Svobodny prosp. 79, Krasnoyarsk, 660041 Russia



Yu. I. Grinshtein
Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky
Russian Federation

MD, PhD, Professor, Head of Chair of Therapy

Partizana Zheleznyaka ul. 1, Krasnoyarsk, 660022 Russia



References

1. Mohr F.W., Morice M.C., Кappetein A.P., et al. Coronary artery bypass graft surgery vs. percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381:629-38. DOI:10.1016/S0140-6736(13)60141-5.

2. McCullough P.A., Vasudevan A., Sathyamoorthy M., et al. Urinary 11-Dehydro-Thromboxane B2 and Mortality in Patients With Stable Coronary Artery Disease. Am J Cardiol. 2017;119(7):972-7. DOI:10.1016/j.amjcard.2016.12.004.

3. Grinshtein Y.I., Kosinova A.A., Grinshtein I.Y., et al. Clinical and laboratory features of patients with ischemic heart disease resistant to acetylsalicylic acid in the perioperative period of coronary artery bypass surgery: results of an open prospective study. Rational Pharmacotherapy in Cardiology. 2016;12(3):265-71 (In Russ.) DOI:10.20996/1819-6446-2016-12-3-265-271.

4. Johnston G.I., Bliss B.A., Newman P.J., McEver P.J. Structure of the human gene encoding granule membrane protein-140, a member of the selectin family of the adhesion receptors for leukocytes. J Biol Chem. 1990;265:21381-5.

5. Johnson R.C., Mayadas T.N., Frenette P.S., et al. Blood cell dynamics in P-selectin-deficient mice. Blood. 1995;86:1106-14.

6. Johnson-Tidey R.R., McGregor J.L., Taylor P.R., Poston R.N. Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1. Am J Pathol. 1994;144:952-61.

7. Tschoepe D., Rauch, U., Schwippert B. Platelet-leukocyte-crosstalk in diabetes mellitus. Horm. Metab Res. 1997;29:631-5. DOI:10.1055/s-2007-979115.

8. Ikeda H., Takajo Y., Ichiki K., et al. Increased soluble form of P-selectin in patients with unstable angina. Circulation. 1995;92:1693-6.

9. Ishiwata S., Tukada T., Nakanishi S., et al. Postangioplasty restenosis: platelet activation and the coagulation-fibrinolysis system as possible factors in the pathogenesis of restenosis. Am Heart J. 1997;133:387-92. DOI:10.1177/1538574416638759.

10. Kaikita K., Ogawa H., Yasue H., et al. Soluble P-selectin is released into the coronary circulation after coronary spasm. Circulation. 1995;92:1726-30. DOI:10.1161/01.CIR.92.7.1726.

11. Burns S.A., Schmidt E.A., Yukhno E.S., et al. Effect of endothelial dysfunction on the prognosis in patients with acute coronary syndrome without ST elevation. Kardiologiia. 2015;4(55): 14-8 (In Russ.)

12. Burns S.A., Schmidt E.A., Kiprina E.S., et al. Predictors of adverse coronary events in patients with acute coronary syndrome with ST-segment elevation, undergone percutaneous coronary interventions. Kardiologiia. 2010;7(50):21-5 (In Russ.)

13. Gurbel P.A., Bliden K.P., Hiatt B.I. et al. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003;107:2908-13. DOI:10.1161/01.CIR.0000072771.11429.83.

14. Kaur R., Singh J., Kaur M. Structural and functional impact of SNPs in P-selectin gene: A comprehensive in silico analysis. Open Life Sciences; 2017;12(1):19-33. DOI:10.1515/biol-2017-0003.

15. Herrmann S., Ricard S., Nicaud V. The P-Selectin Gene is Highly Polymorphic: Reduced Frequency of the Pro715 Allele Carriers in Patients with Myocardial Infarction In: Herrmann S., Ricard S., Nicaud V. Hum Mol Genet. 1998;7(8):1277-84. DOI:10.1093/hmg/7.8.1277.

16. Zhou D.H., Wang Y., Hu W.N., et al. SELP genetic polymorphisms may contribute to the pathogenesis of coronary heart disease and myocardial infarction: a meta-analysis. Mol Biol Rep. 2014;41(5):3369-80. DOI:10.1007/s11033-014-3199-1.

17. Montalescot G., Sechtem U, Achenbach S., et al. ESC Committee for Practice Guidelines. ESC guidelines on the management of stable coronary artery disease. Eur Heart J. 2013;34:2949-3003. DOI:10.1093/eurheartj/eht296.

18. Patent 2413953 of the Russian Federation: IPC G01N 33/86. Grinshtein Y.I., Filonenko I.V., Savchenko A.A. et al. A method for the diagnosis of resistance to acetylsalicylic acid. Patent 2009131242/15; 08/17/2009. Bulletin №7 (In Russ.)

19. Bugert P., Vosberg M., Entelmann M., et al. Polymorphisms in the P-selectin (CD62P) and P-selectin glycoprotein ligand-1 (PSGL-1) genes and coronary heart disease. Clin Chem Lab Med.2004;42(9):997-1004. DOI:10.1515/CCLM.2004.202.

20. Morris D.L., Graham R.R., Erwig L.P., et al. Variation in the upstream region of P-Selectin (SELP) is a risk factor for SLE. Genes Immun. 2009;10(5):404-13. DOI:10.1038/gene.2009.17.

21. Fenoglio C., Scalabrini D., Piccio L., et al. Candidate gene analysis of selectin cluster in patients with multiple sclerosis. J Neurol. 2009;256(5):832-3. DOI:10.1007/s00415-009-5016-7.

22. Podgoreanu M.V., White W.D., Morris R.W., et al.; Perioperative Genetics and Safety Outcomes Study (PEGASUS) Investigative Team. Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery. Circulation. 2006;114(1 Suppl):I275-81. DOI:10.1161/CIRCULATIONAHA.105.001032.

23. Volcik К.А., Ballantyne С.М., Coresh J., et al. Specific P-selectin and P-selectin glycoprotein ligand-1 genotypes/haplotypes are associated with risk of incident CHD and ischemic stroke: The Atherosclerosis Risk in Communities (ARIC) study. Atherosclerosis. 2007;195:e76-e82. DOI:10.1016/j.atherosclerosis.2007.03.007.

24. Zee R.Y.L., Cook N.R., Cheng S., et al. Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis. Human Molecular Genetics. 2004;13(4):389-96. DOI:10.1093/hmg/ddh039.

25. Grinshtein Y.I., Kosinova A.A., Grinshtein I.Y., et al. The prognostic value of combinations of genetic polymorphisms in the ITGB3, ITGA2, and CYP2C19∗2 genes in predicting cardiovascular outcomes after coronary bypass grafting. Testing and Molecular Biomarkers. 2018;22(4):259-65. DOI:10.1089/gtmb.2017.0177.


For citation:


Kosinova A.A., Mongush T.S., Goncharov M.D., Subbotina T.N., Semashchenko K.S., Kochmareva G.Y., Grinshtein Y.I. Study of the Association of V640L (rs6133) Polymorphism in the Platelet P-selectin Gene with Acetylsalicylic Acid Resistance in Patients after Coronary Bypass Surgery. Rational Pharmacotherapy in Cardiology. 2019;15(3):343-348. (In Russ.) https://doi.org/10.20996/1819-6446-2019-15-3-343-348

Views: 118


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)