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Background and purpose: The objective of this study was to determine the influence of 3 vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphisms (-1639G>A, 1173C>T and 3730G>A) on warfarin dose requirement in patients from Mazandaran province, Iran. Materials and methods: A total of 29 patients taking warfarin for at least 3 months and had stable dose requirements were enrolled in the study. DNA samples from these patients were genotyped for polymorphisms in VKORC1 gene and statistical analysis was performed to examine the associations between demographic characteristics (eg, age, sex, weight, height and BMI), genetic factors, and maintenance dose of warfarin Results: In -1639G>A polymorphism, 25 patients (86.2%) were AA, 2 patients (6.9%) were GA and 2 patients (6.9%) were GG genotype. Mean dose of warfarin in patients with AA genotype was lower but their INR was higher than two others genotypes. In 1173C>T, 26 patients (89.7%) were TT, 2 patients (6.9%) were CC and one patient (3.4%) was CT. Mean dose of warfarin in patients with CT genotype was lower but their INR was higher from two others genotypes. In 3730G>A, 28 patients (96.5%) were GG and only one patient (3.5%) was GA. INR in this patient was higher than other genotype. Significant correlation was obtained only between -1639G>A polymorphism and warfarin dose requirement Conclusion: In the present study, we observed genetic polymorphism in all 3 regions. -1639G>A polymorphism was important determinants of warfarin dose requirements in our patients. Correlation between dose requirements and INR with polymorphisms was similar to other studies however, percentage of genotypes in each polymorphism was different from other populations.

Keywords: Polymorphisms, Warfarin, VKORC1, INR

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