The influence of P2Y<sub>12</sub> gene polymorphisms on clopidogrel therapy in patients after percutaneous coronary intervention
Creators: name: Pawlak, Kornel
name: Danielak, Dorota
name: Burchardt, Paweł
name: Kruszyna, Łukasz
name: Karaźniewicz-Łada, Marta
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Science Policy
subject: Hematology

description: <b>Aim:</b> We aimed to define the influence of P2Y12 polymorphisms (rs6801273, rs2046934, and rs6809699), diabetes, hypertension, obesity, hypercholesterolemia, statins intake, and smoking habit on clopidogrel therapy in patients undergoing percutaneous coronary intervention. <b>Materials &amp; methods:</b> We used PCR-RFLP and PCR-ASO for P2Y<sub>12</sub> genotype analysis. The effectiveness of the therapy was measured with the VerifyNow method and defined in platelet reactivity units. <b>Results:</b> Studied polymorphisms had no statistically significant influence on PRU before (PRU<sup>0</sup>) and 6 months (PRU<sup>6</sup>) after the procedure. H1/H1 diabetic carriers had significantly higher PRU<sup>6</sup> values than patients without diabetes. Obese H1/H2 subjects had significantly lower PRU<sup>6</sup> values than H1/H2 non-obese carriers. <b>Conclusion:</b> We found that obesity and diabetes may influence the long-term outcome of antiplatelet therapy. Clopidogrel is a medicine that prevents platelets in the blood from clumping and blocking arteries. When the structure of the protein (e.g., P2Y12), responsible for response to clopidogrel is changed, we can observe less efficient therapy. Said changes can be caused for example by genetic polymorphisms, which are two or more variants of the same gene. This is why we wanted to check the impact of P2Y12 polymorphisms. We also wanted to check the impact of diabetes, high blood pressure, being overweight, high cholesterol blood level, cholesterol-reducing drugs, and smoking habits on clopidogrel treatment in patients after a procedure that unblocks blood vessels of the heart to restore its blood supply (percutaneous coronary intervention). We measured the efficacy of the treatment with platelet reactivity units (PRU). Studying polymorphisms had no impact on treatment efficacy before (PRU0) and 6 months (PRU6) after the medical procedure. We found that diabetes can cause higher platelet reactivity after 6 months of therapy. We noticed that being overweight may also be important, as obese patients had lower platelet reactivity values. This study studied the influence of T744C, G52T, and rs6801273 polymorphism on platelet reactivity units (PRU) values during 6-month clopidogrel therapy. Studied polymorphism was in complete lineage disequilibrium. H1 and H2 haplotypes did not influence PRU values during clopidogrel therapy. rs6801273 polymorphism did not influence PRU values during clopidogrel therapy. Diabetes and H1/H1 combination predisposed to higher PRU values. Obesity and H1/H2 combination predisposed to lower PRU values. A/B/C haplotypes did not influence PRU values during clopidogrel therapy. Hypercholesterolemia, hypertension, and statin intake did not influence PRU values during therapy. Our results may suggest that for different haplotypes, different cofactors can influence antiplatelet therapy.