Impact of RAGE Gene rs۸۰۰۹۶۳۴۹(C>T), rs۱۰۳۵۷۹۸(C>T), and rs۱۸۴۰۰۳(G>T) Polymorphisms on Non-Response to Aspirin in Iraqi Patients with Coronary Artery Disease

Background: Transmembrane multiligand receptor RAGE is a protein found on the surface of cells that binds to the advanced glycation end products. Platelet cyclooxygenase activity is elevated in response to RAGE activation, contributing to the formation of a thrombus.Objectives: To examine the connection between RAGE gene rs۸۰۰۹۶۳۴۹(C>T), rs۱۰۳۵۷۹۸(C>T), and rs۱۸۴۰۰۳(G>T) polymorphisms and resistance to aspirin in CAD patients from Iraq.Patients and methods: Patients with coronary artery disease (CAD) (۱۶۱ males and ۶۴ females) were enrolled in the trial between February ۲۰۲۱ and October ۲۰۲۱. All participants were taking prophylactic Aspirin (۱۰۰ mg). The control group consisted of ۱۳۰ individuals, including ۹۷ males and ۳۳ females, who appeared to be in good health and were not taking aspirin. Serum thromboxane B۲ levels were used to assess the effectiveness of aspirin (TBX۲). Patients were classified as either aspirin sensitive or resistant. The polymorphism of RAGE's most closely related single nucleotide polymorphisms (SNPs) was identified using polymerase chain reaction for amplification of the extracted deoxyribonucleic acid and Sanger's method of sequencing.Results: A total of ۲۲۵ cardiovascular patients compatible with inclusion criteria were enrolled. There were ۱۶۱(۷۱.۶%) male and ۶۴(۲۸.۴%) female patients with a mean age of ۵۶.۸۵±۸.۱۱years old. The statistical analysis revealed ۱۷.۸% (n = ۴۰) aspirin-resistant cases in the study population. Genotypic analysis of our data showed that participants with the T allele of rs۱۸۴۰۰۳(G/T) had an increased prevalence in the aspirin-resistant group compared with the aspirin-sensitive group (p<۰.۰۵). In contrast, for rs۱۰۸۳۵۷۹۸, the frequency was dramatically higher for T alleles in aspirin sensitive group contrasted with the resistant group (p<۰.۰۵). The aspirin-resistant group was found to have significantly greater RAGE levels than the sensitive group.Conclusion: Our results provide evidence that RAGE expression and gene rs۱۰۳۵۷۹۸(C>T), and rs۱۸۴۰۰۳(G>T) polymorphisms could be predictors for CAD patients' resistance to aspirin.

Keywords:

Aspirin resistance , Aspirin nonresponse , RAGE gene polymorphisms , platelet activation