Allele and genotype frequencies of VKORC1 in Birjand population
Administration of warfarin, the most common oral anticoagulant, is usually accompanied with limitations. Anticoagulant effect of warfarin has wide inter-patients variations due to pharmacodynamics, pharmacokinetics and especially pharmacogenetics factors. Polymorphisms of VKORC1 gene is one of the genetic factors influencing adjustment of warfarin dosage. In order to better determine the appropriate dosage of the drug, this study was conducted to find out the allele and genotype frequencies of VKORC1 gene in population of Birjand city.
One hundred-fifteen patients who referred to Imam Reza and Vali-asr hospitals of Birjand city for PT and INR tests, were selected for this experimental study. After genomic DNA extraction, all amplified PCR products of VKORC1 were sequenced to determine the genotypes. Statistical analysis was performed using SPSS software.
The average age of patients was 57.7 ± 12.9, 55 were women and 60 were men. Normal, heterozygous and homozygous mutant genotypes of -1639 G>A variant, had a frequency of 40.3%, 30.5%, 17.5% in men; and 50%, 36.7%, 5% in women, respectively. Regarding 1173C>T variant, normal, heterozygous and homozygous mutant genotypes had a frequency of 38.9%, 38.9%, 22.2% in men; and 52.6%, 40.4%, 7% in women, respectively. Two new mutations as g.3660G> A and g.3565G> T with the frequency of 2.7% and 0.9% in -1639 G>A promoter region of VKORC1 gene were observed. Finally, -1639G and 1173C alleles had a high frequency (68.1% and 62.6%, respectively) in people of Birjand city.
Our results indicate that there are significant differences in the frequency of VKORC1 genetic variants in people of Birjand city compared to other parts of Iran. The ethnic differences can affect sensitivity to warfarin. Therefore, knowing the genotype of the patients before starting warfarin therapy will help to have a precise and efficient therapy.
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