Impact of PCSK9, WDR12, CDKN2A, and CXCL12 Polymorphisms in Jordanian Cardiovascular Patients on Warfarin Responsiveness and Sensitivity

Rasheed K Ibdah; Laith N Al-Eitan; Nasr N Alrabadi; Ayah Y Almasri; Adan H Alnaamneh; Rame H Khasawneh; Mansour A Alghamdi

doi:10.2147/IJGM.S287238

Impact of PCSK9, WDR12, CDKN2A, and CXCL12 Polymorphisms in Jordanian Cardiovascular Patients on Warfarin Responsiveness and Sensitivity

Int J Gen Med. 2021 Jan 14:14:103-118. doi: 10.2147/IJGM.S287238. eCollection 2021.

Authors

Rasheed K Ibdah¹, Laith N Al-Eitan², Nasr N Alrabadi³, Ayah Y Almasri², Adan H Alnaamneh², Rame H Khasawneh⁴, Mansour A Alghamdi^{5

6}

Affiliations

¹ Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
² Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan.
³ Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
⁴ Department of Hematopathology, King Hussein Medical Center (KHMC), Jordan Royal Medical Services (RMS), Amman, Jordan.
⁵ Department of Anatomy, College of Medicine, King Khalid University, Abha, Saudi Arabia.
⁶ Genomics and Personalized Medicine Unit,College of Medicine, King Khalid University, Abha, Saudi Arabia.

Abstract

Background: The main objective of this study is sought to determine the impacts of PCSK9, WDR12, CDKN2A, and CXCL12 polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation and stabilization phases of therapy.

Methods: This study took place at the anticoagulation clinic at Queen Alia Heart Institute (QAHI) in Jordan. DNA samples were collected from 212 cardiovascular patients and 213 healthy controls. Genomic SNPs genotyping was conducted using the MassARRAY System at the Australian Genome Research Facility.

Results: This study assessed 10 polymorphisms (rs11206510 within the PCSK9 gene, rs6725887 and rs7582720 within the WDR12 gene, rs4977574, rs10757278, and rs1333049 within the CDKN2A gene, rs2862116, rs7906426, rs1746048, and rs268322 within the CXCL12 gene) in 212 Jordanian cardiovascular patients. Carriers of CDKN2A rs1333049, rs10757278, and PCSK9 rs11206510 polymorphisms had an increased risk of resistance during the initiation phase of warfarin therapy compared to those who do not carry it, or those who are carrying one polymorphism only (P < 0.05), while carriers of CXCL12 rs7906426 polymorphism had similar increased risk but during the stabilization phase of warfarin therapy (P < 0.05).

Conclusion: Carriers of CXCL12 rs2862116 polymorphism had an increased risk to be warfarin extensive responders compared to those with no or only one polymorphism (P = 0.01). However, the presence of PCSK9 rs11206510 polymorphism affects the warfarin maintenance doses (P ˃ 0.0001).

Keywords: CDKN2A; CXCL1; PCSK9; WDR12; cardiovascular disease; warfarin.

Grants and funding

This project was funded under grant number (203/2014) and supported by the Deanship of Research at Jordan University of Science and Technology.