Association of MIR146A (rs2910164) and MIR499A (rs3746444) gene polymorphisms with markers of thromboinflammation in patients with coronary heart disease after coronary artery bypass grafting

Background. Advances in genomics and proteomics have facilitated the identification of numerous new candidate biomarkers for the diagnosis and prognosis of coronary heart disease (CHD), as well as for predicting adverse cardiovascular events, including post-coronary artery bypass grafting (CABG) outcomes. MicroRNAs represent a promising category of these biomarkers.

Aim: To investigate the association between the rs2910164 polymorphism in the MIR146A gene and the rs3746444 polymorphism in the MIR499A gene with adverse cardiovascular events and general inflammation markers in CHD patients post-CABG.

Material and Methods. This prospective cohort study involved 158 CHD patients with a median age of 63 years [58; 67]. Patients were assessed at three stages: preoperatively, on postoperative days 8–10, and post-discharge. Early in-hospital cardiovascular events were recorded over 8–10 days of hospitalization, and long-term events were tracked for an average of 36.1 ± 10.6 months post-CABG. Comprehensive blood analyses and leukocyte DNA genotyping were conducted preoperatively and on days 8–10 postsurgery. Additionally, flow cytometry and high-sensitivity C-reactive protein (CRP) measurement were performed on a random subset of 102 patients.

Results. The allele frequencies of G and C (rs2910164) were 0.62 and 0.38, respectively, and those of A and G (rs3746444) were 0.83 and 0.17 in the CHD cohort. No significant differences in rare allele prevalence were observed between patients with and without long-term adverse cardiovascular events. Preoperatively, CHD patients with the GG genotype of rs2910164 MIR146A displayed higher plateletplatelet aggregate counts. Post-CABG, this genotype group showed significantly elevated values in platelet-platelet aggregate mean fluorescence intensity (MFI) (33.1 [31.5; 35.75] vs. 30.0 [29.0; 33.13], p = 0.001), MFI of P-selectin-expressing platelets (4.69 [2.05; 6.77] vs. 1.97 [1.49; 2.53], p = 0.002), MFI of P-selectin-expressing platelet–monocyte (6.71 [4.18; 16.4] vs. 4.22 [3.73; 6.14], p = 0.018), and MFI of P-selectin-expressing platelet-platelet aggregates (5.17 [2.47; 7.24] vs. 2.56 [1.7; 2.94], p = 0.003). The erythrocyte sedimentation rate (ESR) was significantly higher in patients with the C allele preoperatively (60.0 [31.0; 89.0] mm/hr vs. 40.0 [27.75; 57.75] mm/hr, p = 0.043).

Conclusions. The presence of rare alleles in rs2910164 (MIR146A) and rs3746444 (MIR499A) was not associated with an increased frequency of in-hospital or long-term adverse cardiovascular events. However, CHD patients with the GG genotype of rs2910164 MIR146A post-CABG exhibited significantly higher MFI in platelet aggregates expressing P-selectin.

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