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    • The Genetic Association of VKORC1 (-1639G<A) Polymorphism with Warfarin Dose Requirements among Egyptian Patients with Venous Thromboembolism

    1Amr Mohamed Salem, 2Mohamed Mohamed Mokhtar, 2Sahar Ahmed El Shafei, 3Omaima Gaber Yassine, 2Eman Farouk Safwat
    1Department of Experimental and Clinical Surgery, Medical Research Institute, Alexandria University, Egypt 2Department of Human Genetics, Medical Research Institute, Alexandria University, Egypt. 3Department of Biomedical informatics and medical statistics, Medical Research Institute, Alexandria University, Egypt

    The aim of the study was to estimate the frequency of VKORC1 (-1639G<A) genotypes and to figure out the effect of “vitamin K epoxide reductase complex subunit 1” (VKORC1) gene polymorphism (-1639G<A) on “warfarin dose requirement” in a sample of Egyptian patients with “venous thromboembolism”.

    Subjects & Methods: A case-control study was carried out in “the Medical Research Institute hospital, Alexandria University, Egypt”. Cases were patients with “venous thromboembolism”(VTE) admitted to the “Experimental and Clinical Surgery Department”. Controls were healthy volunteers without history of VTE. Coming to the hospital as patients’ relatives, within the same age range as cases. Both groups were included in the molecular study using PCR/RFLP technique for detection of (VKORC1) gene polymorphism (-1639G<A).

    Results: The study comprised 37 cases and 47 controls. Twelve patients (32.4%) had GG genotype, 19 patients (51.4%) had AG genotype and 6patients (16.2%) had AA genotype. There was a significant variation in “warfarin maintenance dose “in patients with different genotypes of (VKORC1) at position -1639 suggesting that,(VKORC1) polymorphism has an essential role on the “warfarin maintenance dose” requirement. In addition, a statistical significant difference between VKORC1 (-1639G<A) genotypes and daily “warfarin maintenance dose”was found among cases. No significant difference was detected in Genotype and allele frequencies of VKORC1 (-1639G<A) polymorphism between both cases and controls. Conclusions: In the Egyptian patients with VTE, both VKORC1-1639G and VKORC1-1639A alleles were found with allelic frequency (58 % and 42 %) respectively. There was a significant variation in” warfarin maintenance dose” among patients with different genotypes of (VKORC1) at position -1639, and that (VKORC1) polymorphism has an important influence on the” warfarin dose requirements”.

    Key words:”Venous Thromboembolism”, “warfarin maintenance dose”, VKORC1 (-1639G<A) genotypes, polymorphism.


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