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The Impact of Kinase Insert Domain (KDR) Gene Polymorphism rs2305948 on Clopidogrel Resistance in Iraqi Patients

Ali A Ahmed1,2, Khalid I Amber2, Najah R Hadi1

  • 1Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Kufa.

Acta Informatica Medica : AIM : Journal of the Society for Medical Informatics of Bosnia & Herzegovina : Casopis Drustva Za Medicinsku Informatiku Bih
|January 8, 2021
PubMed

Insights

The rs2305948 polymorphism in the KDR gene is linked to clopidogrel resistance in patients undergoing percutaneous coronary intervention (PCI). This genetic variation also influences metabolic changes like LDL and cholesterol levels.

Area of Science:

  • Cardiovascular Genetics
  • Pharmacogenomics

Background:

  • Clopidogrel is a primary antiplatelet therapy for patients undergoing Percutaneous Coronary Intervention (PCI).
  • Clopidogrel resistance is a significant factor contributing to Major Adverse Cardiovascular Events (MACE) and PCI failure.
  • The Kinase Insert Domain (KDR) gene, encoding VEGFR2, is implicated in atherogenesis and Coronary Artery Disease (CAD) pathogenesis, with the rs2305948 single nucleotide polymorphism (SNP) being of interest.

Purpose of the Study:

  • To investigate the association between the KDR gene polymorphism rs2305948 and clopidogrel resistance in patients undergoing elective PCI.
  • To explore the influence of this SNP on metabolic factors in the study population.

Main Methods:

  • A case-control study involving 324 patients undergoing elective PCI, categorized into clopidogrel resistance (CR) and non-clopidogrel resistance (NCR) groups.
  • Measurement of serum lipids, VEGFR2 levels, BMI, and platelet count.
  • Genotyping for the rs2305948 polymorphism using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and confirmed by gene sequencing.

Main Results:

  • Significant association found between the rs2305948 polymorphism and clopidogrel resistance in the CR group compared to the NCR group across multiple genetic models.
  • The T allele of rs2305948 showed a significant correlation with elevated LDL, cholesterol, and serum VEGFR2 levels in dominant and co-dominant models.
  • Genotyping results were consistent with Hardy-Weinberg equilibrium (HWE).

Conclusions:

  • The rs2305948 SNP in the KDR gene is significantly associated with the occurrence of clopidogrel resistance.
  • This genetic polymorphism may play a role in the development of associated metabolic alterations, impacting patient outcomes post-PCI.
Abstract

Keywords:
Clopidogrel resistanceVEGFR2

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