the study of aassociation between cytochrome p450 2 c9 and vitamin k epoxide reductase complex subunit 1 polymorphisms with warfarin dose among iranian patients
نویسندگان
چکیده
background: warfarin is a common anticoagulant drug that has a narrow therapeutic index; higher dose causes excessive bleeding and lower dose leads to cerebrovascular clotting and stroke in patients. genetic factors that have been associated with warfarin response are the genes of cytochrome p450 2c9 (cyp2c9), which metabolize the more active s-enantiomer of warfarin, and vitamin k epoxide reductase (vkor), the target site for warfarin. the present study was conducted to investigate the association between cyp2c9*2, cyp2c9*3 and vkorc1 (-1639 g>a) polymorphisms with warfarin daily dose on 118 iranian patients under warfarin treatment. materials and methods: this study is comprised of 118 iranian patients on warfarin treatment who attended the pt clinic. genotyping of cyp2c9*2, cyp2c9*3 and vkorc1 (-1639 g>a) was performed by pcr-rflp method. multiple regression model was performed for statistical analyses and p<0.05 was considered as significance level. results: the allelic frequencies of cyp2c9*2 and cyp2c9*3 were 19% and 7%, respectively. patients with ≥1 cyp2c9 variant allele had a significantly lower mean warfarin daily dose compared with patients with the wild-type genotype. the allelic frequencies of vkorc1 were 14.4%, 57.6% and 27.9% for gg, ga, and aa genotypes, respectively. the mean (sd) warfarin daily dose in patients with the vkorc1 (–1639) gg genotype was significantly higher than ga and aa patients. conclusion: cyp2c9*2, cyp2c9*3 and vkorc1 (-1639 g>a) polymorphisms had significant association with warfarin daily dose. furthermore, the daily warfarin dose was not influenced by age, height, weight and sex.
منابع مشابه
Association between Cytochrome P450 2 C9 and Vitamin K Epoxide Reductase Complex Subunit 1 Polymorphisms with Warfarin dose among Iranian Patients
Background: Warfarin is a common anticoagulant drug that has a narrow therapeutic index; higher dose causes excessive bleeding and lower dose leads to cerebrovascular clotting and stroke in patients. Genetic factors that have been associated with warfarin response are the genes of cytochrome P450 2C9 (CYP2C9), which metabolize the more active S-enantiomer of warfarin, and vitamin K epoxide redu...
متن کاملassociation between cytochrome p450 2 c9 and vitamin k epoxide reductase complex subunit 1 polymorphisms with warfarin dose among iranian patients
background: north of iran is amongst high incidence rate areas of gastric carcinoma where environmental carcinogenic compounds especially agricultural pesticides are massively used. cytochrome p450 2e1 (cyp2e1) enzyme metabolically activates a large number of low molecular mass xenobiotics. the polymorphic nature of cyp2e1 gene control elements is associated with interindividual differences for...
متن کاملRegulatory polymorphism in vitamin K epoxide reductase complex subunit 1 (VKORC1) affects gene expression and warfarin dose requirement.
Warfarin dose requirements have been associated with 2 main haplotypes in VKORC1, but the responsible polymorphisms remain unknown. To search for regulatory polymorphisms, we measured allelic mRNA expression of VKORC1 in human liver, heart, and B lymphocytes. The observed 2-fold allelic mRNA expression imbalance narrowed possible candidate SNPs to -1639G>A and 1173C<T. This genotype effect was ...
متن کاملThe Contribution of VKORC1 and CYP2C9 Genetic Polymorphisms and Patients’ Demographic Characteristics with Warfarin Maintenance Doses: A Suggested Warfarin Dosing Algorithm
The requirement of varying doses of warfarin for different individuals can be explained by environmental and genetic factors. We evaluated the frequency of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) variants together with patientdemographic characteristics and investigated their association with warfarin dose requirement with the ob...
متن کاملThe Contribution of VKORC1 and CYP2C9 Genetic Polymorphisms and Patients’ Demographic Characteristics with Warfarin Maintenance Doses: A Suggested Warfarin Dosing Algorithm
The requirement of varying doses of warfarin for different individuals can be explained by environmental and genetic factors. We evaluated the frequency of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) variants together with patientdemographic characteristics and investigated their association with warfarin dose requirement with the ob...
متن کاملCytochrome P450 (CYP2C9*2,*3) & vitamin-K epoxide reductase complex (VKORC1 -1639G<A) gene polymorphisms & their effect on acenocoumarol dose in patients with mechanical heart valve replacement
BACKGROUND & OBJECTIVES Studies have demonstrated the effect of CYP2C9 (cytochrome P450) and VKORC1 (vitamin K epoxide reductase complex) gene polymorphisms on the dose of acenocoumarol. The data from India about these gene polymorphisms and their effects on acenocoumarol dose are scarce. The aim of this study was to determine the occurrence of CYP2C9*2,*3 and VKORC 1 -1639G>A gene polymorphism...
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عنوان ژورنال:
research in molecular medicineجلد ۴، شماره ۴، صفحات ۳۸-۴۴
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