The Prognostic Value of Combinations of Genetic Polymorphisms in the ITGB3, ITGA2, and CYP2C19*2 Genes in Predicting Cardiovascular Outcomes After Coronary Bypass Grafting

Grinshtein, Yu. I.; Косинова, А. А.; Grinshtein, I. Yu.; Субботина, Т. Н.; Савченко, А. А.

doi:10.1089/gtmb.2017.0177

Cited by 11 publications

(8 citation statements)

References 33 publications

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“…Platelet’s function may vary by 30% due to genetic diversity. Genetic polymorphisms of platelet receptors have associations with high risk of bleeding and thrombosis events [ 17 , 35 , 36 ]. Genetic factors of glycoprotein GPIIb/IIIa receptors, fibrinogen, prothrombin, VWF, factor V, factor VII, factor XIII and plasminogen activator inhibitor-1 have major role in the process of hemostasis and are associated with side effects in cardiovascular events.…”

Section: Discussionmentioning

confidence: 99%

Association of Genetic Polymorphisms with Complications of Implanted LVAD Devices in Patients with Congestive Heart Failure: A Kazakhstani Study

Zhalbinova

Rakhimova

Kozhamkulov

et al. 2022

JPM

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The left ventricular assist device (LVAD) is one of the alternative treatments for heart failure (HF) patients. However, LVAD support is followed by thrombosis, and bleeding complications which are caused by high non-physiologic shear stress and antithrombotic/anticoagulant therapy. A high risk of complications occurs in the presence of the genotype polymorphisms which are involved in the coagulation system, hemostasis function and in the metabolism of the therapy. The aim of the study was to investigate the influence of single-nucleotide polymorphisms (SNP) in HF patients with LVAD complications. We analyzed 21 SNPs in HF patients (n = 98) with/without complications, and healthy controls (n = 95). SNPs rs9934438; rs9923231 in VKORC1, rs5918 in ITGB3 and rs2070959 in UGT1A6 demonstrated significant association with HF patients’ complications (OR (95% CI): 3.96 (1.42–11.02), p = 0.0057), (OR (95% CI): 3.55 (1.28–9.86), p = 0.011), (OR (95% CI): 5.37 (1.79–16.16), p = 0.0056) and OR (95% CI): 4.40 (1.06–18.20), p = 0.044]. Genotype polymorphisms could help to predict complications at pre- and post-LVAD implantation period, which will reduce mortality rate. Our research showed that patients can receive treatment with warfarin and aspirin with a personalized dosage and LVAD complications can be predicted by reference to their genotype polymorphisms in VKORC1, ITGB3 and UGT1A6 genes.

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Section: Discussionmentioning

confidence: 99%

Association of Genetic Polymorphisms with Complications of Implanted LVAD Devices in Patients with Congestive Heart Failure: A Kazakhstani Study

Zhalbinova

Rakhimova

Kozhamkulov

et al. 2022

JPM

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“…В том числе, и по той причине, что один полиморфизм гена адгезивной молекулы в сложном каскаде гемостаза и воспаления может быть компенсирован работой множеством других. В нашей предыдущей работе показано, что редкая аллель полиморфизма отдельно взятого тромбоцитарного рецептора не приводила к развитию неблагоприятных исходов после КШ, тогда как носительство редких аллелей нескольких полиморфизмов увеличивало риски кардиоваскулярных событий [25].…”

Section: Discussionunclassified

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

Косинова

Монгуш

Goncharov

et al. 2019

Racionalʹnaâ farmakoterapiâ v kardiologii

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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 homozygotesof 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.

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“…This phenomenon was defined as ASA resistance. Single nucleotide polymorphisms, miRNAs, metabolic syndrome, inflammation, malabsorption in the gastrointestinal tract and some others were considered as reasons for the development of ASA resistance [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Resistance to Acetylsalicylic Acid in Patients with Coronary Heart Disease Is the Result of Metabolic Activity of Platelets

et al. 2020

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Sensitivity to acetylsalicylic acid (ASA) is important in the treatment of patients with coronary heart disease (CHD) after coronary artery bypass grafting (CABG). Patients were divided into ASA sensitive (sASA) and ASA resistant (rASA) by the activity of platelet aggregation induced arachidonic acid (ARA) together with ASA. Induced platelet aggregation activity was studied in sASA and rASA patients with CHD before and after CABG. The level of synthesis of primary and secondary reactive oxygen species (ROS) by platelets was determined using chemiluminescent analysis. The activity of NAD- and NADP-dependent dehydrogenases in platelets was determined by the bioluminescent method. It was found that the aggregation activity of platelets depended on the sensitivity of CHD patients to ASA and decreased during postoperative ASA therapy. The most pronounced differences in metabolic parameters of platelets in sASA and rASA patients were detected by Nox2 activity. The synthesis of secondary ROS by platelets of CHD patients did not depend on the sensitivity of patients to ASA but increased during postoperative treatment with ASA. The activity of NAD(P)-dependent dehydrogenases in platelets did not differ in sASA and rASA patients with CHD.

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The Prognostic Value of Combinations of Genetic Polymorphisms in the ITGB3, ITGA2, and CYP2C19*2 Genes in Predicting Cardiovascular Outcomes After Coronary Bypass Grafting

Abstract: Carriage of a combination of mutant alleles in multiple genes including ITGB3+CYP2C192 or CYP2C192 + ITGA2 or CYP2C19*2 are possible predictors of CVE in patients after CABG.

Cited by 11 publications

References 33 publications

Association of Genetic Polymorphisms with Complications of Implanted LVAD Devices in Patients with Congestive Heart Failure: A Kazakhstani Study

Association of Genetic Polymorphisms with Complications of Implanted LVAD Devices in Patients with Congestive Heart Failure: A Kazakhstani Study

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

Resistance to Acetylsalicylic Acid in Patients with Coronary Heart Disease Is the Result of Metabolic Activity of Platelets

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The Prognostic Value of Combinations of Genetic Polymorphisms in the ITGB3, ITGA2, and CYP2C19*2 Genes in Predicting Cardiovascular Outcomes After Coronary Bypass Grafting

Abstract: Carriage of a combination of mutant alleles in multiple genes including ITGB3+CYP2C19*2 or CYP2C19*2 + ITGA2 or CYP2C19*2 are possible predictors of CVE in patients after CABG.

Cited by 11 publications

References 33 publications

Association of Genetic Polymorphisms with Complications of Implanted LVAD Devices in Patients with Congestive Heart Failure: A Kazakhstani Study

Association of Genetic Polymorphisms with Complications of Implanted LVAD Devices in Patients with Congestive Heart Failure: A Kazakhstani Study

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

Resistance to Acetylsalicylic Acid in Patients with Coronary Heart Disease Is the Result of Metabolic Activity of Platelets

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Abstract: Carriage of a combination of mutant alleles in multiple genes including ITGB3+CYP2C192 or CYP2C192 + ITGA2 or CYP2C19*2 are possible predictors of CVE in patients after CABG.