ASSOCIATION OF THE T1565C (RS5918) POLYMORPHISM IN THE INTEGRINE-Β3 (ITGB3) GENE WITH INTERVENTION CHARACTERISTICS, PERIPROCEDURAL COMPLICATIONS, AND LONG-TERM PROGNOSIS AFTER PLANNED ENDOVASCULAR MYOCARDIAL REVASCULARIZATION Running title: ITGB3 polymorphism: interventions, complications, and prognosis

Highlights

• Polymorphism rs5918 in the ITGB3 gene is associated with procedural features, acute complications and long-term prognosis after elective endovascular myocardial revascularization. In the group of patients with stable coronary artery disease who have indications for elective PCI, the presence of the T allele is associated with concomitant carbohydrate metabolism disorders, multivessel coronary artery disease, implantation of 2 or more stents, and a lower rate of achieving complete myocardial revascularization during index PCI.
• The presence of the minor allele C and the homozygous genotype CC is associated with greater comorbidity in patients, features of coronary atherosclerosis in the form of more frequent hemodynamically significant lesions of the left main coronary artery and anterior descending artery, more frequent achievement of complete myocardial revascularization and a lower value of the residual SYNTAX index with the implantation of a smaller number of stents during the index intervention. In the recessive model (TT + TC/CC), the presence of the minor homozygous CC genotype increased the odds of developing periprocedural AKI by 7.2 times (OR 7.200; 95% CI [1.827–28.379], p = 0.011). Five years after the index PCI, patients with the minor C allele had worse renal function than those with the T allele (GFR ≤ 60 ml/min/1.73 m² in 19%, 36%, and 40% of patients in the groups with the TT, TC, and CC genotypes, respectively, p = 0.04).

Aim. To study the association of the T1565C (rs5918) polymorphism in the ITGB3 gene with the characteristics of interventions, periprocedural complications and long-term prognosis of patients after elective endovascular myocardial revascularization.

Methods. Polymorphic variants of the single nucleotide polymorphism T1565C (rs5918) in the ITGB3 gene were identified in 364 patients undergoing elective PCI. We studied the characteristics of coronary artery disease and the interventions performed, and also assessed the frequency of acute complications, late (5-year) adverse events, and the dynamics of renal function in the acute and late periods in groups of patients with different genotypes of the rs5918 polymorphism in the ITGB3 gene. Contingency tables and odds ratio (OR) calculations were used to assess the association of this polymorphism with endpoints.

Results. The minor allele 1565C and the 1565CC of the polymorphism T1565C (rs5918) in the ITGB3 gene genotype are associated with more frequent hemodynamically significant stenosis of the left main coronary artery (4.4, 6.9 and 30% in the TT, TC and CC groups, respectively, p = 0.003) and the anterior descending artery (79, 66.7 and 100% in the TT, TC and CC groups, respectively, p = 0.01), more frequent achievement of complete myocardial revascularization (54.4, 70.6, 70% in the TT, TC and CC groups, respectively, p = 0.01) and a lower residual SYNTAX index (4.1 ± 6.7 (0–43.5); 2.9 ± 6.2 (0–28.5) and 2.4 ± 4.6 (0–14) in the TT, TC and CC groups, respectively, p = 0.02) with implantation of a smaller number of stents. In addition, an association was found between the minor 1565CC genotype with acute periprocedural kidney injury (OR 7.200; 95% CI [1.827–28.379], p = 0.011) and deterioration of renal function 5 years after index PCI (SCF ≤ 60 ml/min/1.73 m² in 19, 36 and 40% in the TT, TC and CC groups, respectively, p = 0.04).

Conclusion. Under conditions of dual antiplatelet therapy, selected taking into account the residual platelet reactivity according to the aggregogram data, no association was found between the T1565C (rs5918) polymorphism in the ITGB3 gene and acute periprocedural myocardial injury and long-term cardiovascular complications. Polymorphism rs5918 in the ITGB3 gene is associated with acute periprocedural kidney injury and decreased renal function in the late period.

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