Study of Association between RAGE Gene Polymorphism rs2070600 (G82S) and Aspirin Resistance in Coronary Artery Disease Iraqi Patients with and without Type 2 Diabetes

Abstract

Background: Despite Aspirin efficacy in cardiovascular disease, several patients on Aspirin therapy continue suffering thrombotic complications. Aspirin  resistance phenomena is usually accompanied by potentially harmful consequences. The etiology is likely to be multifactorial. Several evidences suggested that genetic factors contribute significantly to the risk of aspirin resistance. RAGE is a multiligand cell surface receptor. It is expressed in many cells including platelets. RAGE/ligand interaction has been evidenced to play a major role in oxidative stress mediated complications in coronary artery disease (CAD) and diabetes mellitus (DM). RAGE is implicated in platelet activation under pathological conditions. A functional polymorphism rs2070600 in the gene coding RAGE might modulate its receptor function. It is associated with enhanced ligand binding, leading to an enhanced receptor signaling and increased the ligand-stimulated generation of inflammatory mediators. Objectives: The present study is aimed to evaluate the association between Receptor of Advanced Glycation End product (RAGE) – gene polymorphisms rs2070600 (G82S) and Aspirin resistance in coronary artery disease Iraqi patients with and without type 2 diabetes, and to detect the prevalence of Aspirin resistance in the studied population.
Patients and method: From February 2021 to October 2021, diabetic and non diabetic coronary artery disease (CAD) patients 225 (161 males, 64 females) already they were on aspirin 100 mg as prophylaxis were enrolled in a cross-sectional study, in addition to 130 (97 males,33 females) apparently healthy participants not taking Aspirin served as control group. The response to Aspirin was evaluated by measurement the serum level of thromboxane B2 (TBX2), which is the more stable and measurable metabolite due activity of cyclooxygenase-1 (COX-1) enzyme that directly inhibited by Aspirin. Accordingly, the patients were divided into two groups: sensitive and resistant to aspirin. Polymerase chain reaction amplification of the extracted deoxyribonucleic acid, and sequencing by Sanger method were used to identify the polymorphism of mostly related single nucleotide polymorphism (SNP) of RAGE (rs2070600).
Results: Prevalence of Aspirin resistance for all patients was 17.8%. For non diabetic CAD patients the prevalence was 16.1%, while for diabetic CAD patients the prevalence was relatively higher (19.6%). For rs2070600(G>A) frequency, there was no significant difference between resistant and sensitive groups (p value >0.05). However, a significantly higher serum levels of RAGE were detected in Aspirin- resistant groups compared with sensitive one in CAD patient; whether they were diabetic or non-diabetic, and the study showed a highly significant positive correlation between serum levels of RAGE and CRP. Conclusion: The prevalence of Aspirin resistance among the studied Iraqi patients was relatively high and risky and could represent a challenge in considering Aspirin therapy for CAD patients by the specialists to be aware about such issue. However, our study didn’t show significant association between Gly82Ser variants (rs2070600) with the risk of Aspirin resistance.