Polymorphism Detection of VKORC1 (Vitamin K Epoxide Reductase Complex, Subunit 1) Gene for Warfarin Dose Adjustment in Egyptian Patients with Budd Chiari and/or Portal Vein Thrombosis: A Single Center Experience

Abstract

Background Budd–Chiari syndrome is a heterogeneous group of disorders characterized by hepatic venous outflow obstruction at the level of the hepatic venules, the large hepatic veins, the inferior vena cava till its junction with the right atrium. The classic triad of abdominal pain, ascites, and hepatomegaly is observed in the vast majority of patients with Budd-Chiari syndrome, but it is nonspecific. Warfarin was introduced into clinical practice in the 1950s, and has been the most widely prescribed oral anti-coagulant for prevention and treatment of thrombotic diseases despite its significant side effects as (bleeding tendency, drug drug interaction). Vitamin K epoxide reductase complex subunit1 (VKORC1), a membrane protein located in hepatocytes, has an important role in the anabolism of vitamin K, which is essential for blood coagulation. Objectives The aim beyond this study is to evaluate effect of the allelic frequency of the VKORC1 (G1639A) polymorphic genes by real time PCR on response of Egyptian patients with Budd–Chiari syndrome or PVT to Warfarin. Patients and Methods The studied patients were selected from patients presented to Budd chiari study group clinic.tropical medicine department in Ain Shams University hospitals. Within 6 months from july 2020 to December 2020, total number of cases during the study period was 50 cases fulfilling the inclusion criteria Results The mean age of the patients was (32.40 ± 9.69) slightly more common in males. The chronic presentation represented 60% of the patients and the acute represented 32%.The most common cause of budd chiarri syndrome was MTHFRD (52%) followed by FVLM (36%) then Primary ant phospholipid antibody syndrome (26%). Patients with the −1639 promoter polymorphism GG genotype had lower dose requirements, whereas the AG/AA genotypes had higher dose. Conclusion Identifying these polymorphisms in patients prior to starting the therapy may help clinicians choose the appropriate warfarin dose & decrease its adverse effects.