Abstract
BackgroundClopidogrel is an antiplatelet therapy that is widely used in pre and post percutaneous (PCI) coronary intervention procedures to prevent platelet aggregation and stent restenosis. However, there is a wide inter-individual variation in clopidogrel response and some patients showed resistance against the activity of Clopidogrel. Kinase insert domain receptor (KDR) gene is responsible for the transcription of vascular endothelial growth factor receptor 2 (VEGFR2) that plays a major role in the cardiovascular diseases (CVDs) and platelet aggregation. The aim of this study was to find out the association of KDR rs1870377 genotype with clopidogrel resistance (CR) in CVD patients, of Iraqi Arabic origin, hospitalized for elective PCI. Materials and methodsThis study was a case-control study with a total of 324 PCI patients. Those patients were classified into 213 patients with non-clopidogrel resistant and 111 patients with CR, depending on the analysis of platelet activity phenotype after clopidogrel administration. KDR rs1870377 was genotyped for all patients using polymerase chain reaction-restriction fragment length polymorphism technique and confirmed by DNA Sänger sequencing through applying Biosystems Model (ABI3730x1). ResultsKDR rs1870377 SNP is strongly associated (Chi-sqaure, p vale <0.05) with CR under dominant, co-dominant and recessive models. Additionally, A allele in the rs1870377 SNP may have an impact on the serum levels of VEGFR2 and low density lipoprotein. ConclusionsKDR rs1870377 SNP is a potential genetic biomarker of CR among CVD patients of Iraqi Arabic origin. Further clinical studies, with larger sample, are required to confirm the findings of this study.
Highlights
Clopidogrel exhibits significant variability in its response ranging from over activity that may cause bleeding to loss of function that causes significant adverse cardiovascular events [1]
Clopidogrel is still the most common irreversible antagonist of adenine diphosphate receptor used to inhibit platelet aggregation in percutaneous coronary intervention (PCI) and cardiovascular disease (CAD) patients [2], it has been reported that the main reason for the failure of PCI is the formation of platelet aggregation despite the use of clopidogrel in the treatment regimen [3]
Recent studies clarified the strong association of atherosclerosis and the occurrence of CAD with a genetic variant in the Kinase Insert Domain Receptor (KDR) gene, the rs1870377 variant that responsible for transcription of vascular endothelial growth factor 2 (VEGFR2) receptor in vascular endothelial cells [6]
Summary
Clopidogrel exhibits significant variability in its response ranging from over activity that may cause bleeding to loss of function that causes significant adverse cardiovascular events [1]. A nucleotide substitute of thymine (T) at the 1719 position on exon 11, by adenine (A), results in a variant (rs1870377) due to a missense mutation followed by an amino acid substitution Such a substitution causes a dysfunction of the VEGFR2 receptor [10]. Kinase insert domain receptor (KDR) gene is responsible for the transcription of vascular endothelial growth factor receptor 2 (VEGFR2) that plays a major role in the cardiovascular diseases (CVDs) and platelet aggregation. The aim of this study was to find out the association of KDR rs1870377 genotype with clopidogrel resistance (CR) in CVD patients, of Iraqi Arabic origin, hospitalized for elective PCI. Materials and methods: This study was a case-control study with a total of 324 PCI patients Those patients were classified into 213 patients with non-clopidogrel resistant and 111 patients with CR, depending on the analysis of platelet activity phenotype after clopidogrel administration. With larger sample, are required to confirm the findings of this study
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