Leyla Pourgholi1, Hamidreza Goodarzynejad2, Ali Mandegary3, Shayan Ziaee4, Azita Hajhosseini Talasaz5, Arash Jalali2, Mohammadali Boroumand6. 1. Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran, Iran; Department of Pharmacology & Toxicology, School of Pharmacy, Kerman University of Medical Sciences, P.O. Box 7616911319, Kerman, Iran. 2. Department of Cardiac Research, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran, Iran. 3. Department of Pharmacology & Toxicology, School of Pharmacy, Kerman University of Medical Sciences, P.O. Box 7616911319, Kerman, Iran; Gastroenterology and Hepatology Research Center, Afzalipour's Hospital, Imam Highway, P.O. Box 7616913911, Kerman, Iran. 4. Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran, Iran. 5. Department of Cardiac Research, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran, Iran; Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences. 6. Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran, Iran. Electronic address: maboroumand@yahoo.com.
Abstract
BACKGROUND: Bleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients. METHODS: A total of 552 warfarin treated patients who maintained on a target INR level of 2.0-3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics. Ninety-two bleeding events were observed in 87 patients. The presences of the examined polymorphisms were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). RESULTS: Patients with the T allele in NQO1*2 (CT or TT genotypes) had a higher risk of bleeding than patients with the CC genotype (adjusted OR: 2.25, 95% CI: 1.37 to 3.70, P=0.001). Those who were carriers of CYP2C9 one-variant haplotypes (*1/*2 or *1/*3) were also found to be associated with the higher risk of bleeding events. Compared to reference group (*1/*1), the odds of bleeding increased for carriers of one variant allele (*1/*2 or *1/*3) (adjusted OR: 1.75, 95% CI: 1.03 to 2.97, P=0.039). Variant VKORC1, Factor VII, and EPHX1 genotypes were not significantly associated with the risk of bleeding events. CONCLUSION: The SNP C609T within NQO1 and haplotypes of CYP2C9 (1*2 or 1*3) are independently associated to bleeding complications of warfarin at normal INR. Further studies are required to confirm such associations in diverse racial and ethnic populations.
BACKGROUND:Bleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients. METHODS: A total of 552 warfarin treated patients who maintained on a target INR level of 2.0-3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics. Ninety-two bleeding events were observed in 87 patients. The presences of the examined polymorphisms were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). RESULTS:Patients with the T allele in NQO1*2 (CT or TT genotypes) had a higher risk of bleeding than patients with the CC genotype (adjusted OR: 2.25, 95% CI: 1.37 to 3.70, P=0.001). Those who were carriers of CYP2C9 one-variant haplotypes (*1/*2 or *1/*3) were also found to be associated with the higher risk of bleeding events. Compared to reference group (*1/*1), the odds of bleeding increased for carriers of one variant allele (*1/*2 or *1/*3) (adjusted OR: 1.75, 95% CI: 1.03 to 2.97, P=0.039). Variant VKORC1, Factor VII, and EPHX1 genotypes were not significantly associated with the risk of bleeding events. CONCLUSION: The SNP C609T within NQO1 and haplotypes of CYP2C9 (1*2 or 1*3) are independently associated to bleeding complications of warfarin at normal INR. Further studies are required to confirm such associations in diverse racial and ethnic populations.
Authors: Huma Shafique; Naeem Mahmood Ashraf; Amir Rashid; Asifa Majeed; Tayyaba Afsar; Ann K Daly; Ali Almajwal; Nawaf W Alruwaili; Azmat Ullah Khan; Suhail Razak Journal: Front Cardiovasc Med Date: 2022-06-10