Association of KDR rs1870377 genotype with clopidogrel resistance in patients with post percutaneous coronary intervention

Wajdy Al Awaida; Ali A Ahmed; Asia Ali Hamza; Khalid I Amber; Hamzeh J Al-Ameer; Yazun Jarrar; Ghizal Fatima; Ahmed O Maslat; Yulia Gushchina; Omar Al Bawareed; Najah R Hadi

doi:10.1016/j.heliyon.2021.e06251

Association of KDR rs1870377 genotype with clopidogrel resistance in patients with post percutaneous coronary intervention

Heliyon. 2021 Feb 16;7(2):e06251. doi: 10.1016/j.heliyon.2021.e06251. eCollection 2021 Feb.

Authors

Affiliations

¹ Department of Biology and Biotechnology, American University of Madaba, Madaba 11821, Jordan.
² Department of Pharmacology and Therapeutics, College of Medicine, University of Kufa, Iraq.
³ Department of Biochemistry, College of Medicine, University of Kufa, Iraq.
⁴ Al Najaf Center for Cardiovascular Surgery and Cardiac Catheterization in AL-Sadder Teaching Hospital in Al Najaf Al-Ashraf Governorate, Iraq.
⁵ Department of Pharmacy, College of Pharmacy, Alzaytoonah University of Jordan, 11734 Amman, Jordan.
⁶ Era's Medical College, Era University, Lucknow, India.
⁷ Department of Biological Sciences, Yarmouk University, Irbid, Jordan.
⁸ Department of General and Clinical Pharmacology, Рeoples' Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, Moscow, 117198, Russian Federation.
⁹ Department of Normal Physiology, Рeoples' Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, Moscow, 117198, Russian Federation.

Abstract

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.

Keywords: Clopidogrel resistance; KDR; Post percutaneous coronary intervention; SNP; VEGFR2.