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Association of KDR rs1870377 genotype with clopidogrel resistance in patients with post percutaneous coronary
Wajdy Al Awaida1, Ali A Ahmed2, Asia Ali Hamza3
1Department of Biology and Biotechnology, American University of Madaba, Madaba 11821, Jordan.
Insights
The KDR rs1870377 gene variant is linked to clopidogrel resistance in Iraqi cardiovascular disease patients undergoing PCI. This finding may help personalize antiplatelet therapy.
Area of Science:
- Pharmacogenomics
- Cardiovascular Genetics
- Molecular Biology
Background:
- Clopidogrel is a vital antiplatelet medication used after percutaneous coronary intervention (PCI) to prevent blood clots.
- Individual responses to clopidogrel vary significantly, leading to clopidogrel resistance in some patients.
- The Kinase Insert Domain Receptor (KDR) gene, encoding VEGFR2, is crucial in cardiovascular health and platelet function.
Purpose of the Study:
- To investigate the association between the KDR rs1870377 single nucleotide polymorphism (SNP) and clopidogrel resistance (CR).
- To evaluate this association in cardiovascular disease (CVD) patients of Iraqi Arabic origin undergoing elective PCI.
Main Methods:
- A case-control study involving 324 PCI patients, categorized into clopidogrel-resistant (111) and non-resistant (213) groups based on platelet activity.
- Genotyping of the KDR rs1870377 SNP was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
- Sequencing confirmation of the KDR rs1870377 genotype was done using DNA Sanger sequencing.
Main Results:
- A significant association was found between the KDR rs1870377 SNP and clopidogrel resistance across dominant, co-dominant, and recessive genetic models (p<0.05).
- The 'A' allele of rs1870377 may influence serum levels of VEGFR2 and low-density lipoprotein (LDL).
Conclusions:
- The KDR rs1870377 SNP is identified as a potential genetic biomarker for predicting clopidogrel resistance in Iraqi CVD patients.
- Further large-scale clinical studies are warranted to validate these findings and their clinical implications.
Background:
Clopidogrel 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 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. 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).
Results:
KDR 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.
Conclusions:
KDR 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.
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