Scientific Journal of

Abstract

Background and Objectives

Warfarin and other anticoagulant medications like Coumadin are widely prescribed by physicians to prevent ischemic events. A variety of factors such as sex, age and weight can affect warfarin dosage requirements. A clinical effect of warfarin depends on highly polymorphic drug-metabolizing (CYP2C9) enzymes. The objective of this study was to investigate the impact of CYP2C9*2, CYP2C9*3 polymorphisms on the variability of warfarin dosage requirements in Iranian population that were under warfarin therapy for different reasons.

Materials and Methods

The study included 100 patients with the mean age of 61.3 years. The restriction fragment length polymorphism method was used to identify polymorphisms of CYP2C9 (*1, *2, *3) in Iranian patients with ischemic heart disease in Peyvand Laboratory.

Results

Two-thirds (68.42%) of the patients had the wild-type (WT) CYP2C9*1*1 genotype 10.53%, 18.95%, and 2.1% of the patients had CYP2C9 *1*2, *1*3, and *2*3 genotype, respectively. WT CYP2C9*1*1 genotype was associated with a higher daily warfarin dosage (4.58 ± 1.57 mg/day  p= 0.02) as compared to other CYP2C9 genotypes.

Conclusions

The Iranian study sample is characterized by high frequency *1*1 genotypes that determine a higher warfarin-loading dose. Analysis of CYP2C9 gene variants allows the prediction of warfarin dosage. These results can be used to individualize treatment with warfarin in Iranian patients.

Key words: Warfarin, Genetic Polymorphism, CYP2C9 protein٬ human, Vitamin K

Abstract

Background and Objectives

Warfarin and other anticoagulant medications like Coumadin are widely prescribed by physicians to prevent ischemic events. A variety of factors such as sex, age and weight can affect warfarin dosage requirements. A clinical effect of warfarin depends on highly polymorphic drug-metabolizing (CYP2C9) enzymes. The objective of this study was to investigate the impact of CYP2C9*2, CYP2C9*3 polymorphisms on the variability of warfarin dosage requirements in Iranian population that were under warfarin therapy for different reasons.

Materials and Methods

The study included 100 patients with the mean age of 61.3 years. The restriction fragment length polymorphism method was used to identify polymorphisms of CYP2C9 (*1, *2, *3) in Iranian patients with ischemic heart disease in Peyvand Laboratory.

Results

Two-thirds (68.42%) of the patients had the wild-type (WT) CYP2C9*1*1 genotype 10.53%, 18.95%, and 2.1% of the patients had CYP2C9 *1*2, *1*3, and *2*3 genotype, respectively. WT CYP2C9*1*1 genotype was associated with a higher daily warfarin dosage (4.58 ± 1.57 mg/day  p= 0.02) as compared to other CYP2C9 genotypes.

Conclusions

The Iranian study sample is characterized by high frequency *1*1 genotypes that determine a higher warfarin-loading dose. Analysis of CYP2C9 gene variants allows the prediction of warfarin dosage. These results can be used to individualize treatment with warfarin in Iranian patients.

Key words: Warfarin, Genetic Polymorphism, CYP2C9 protein٬ human, Vitamin K

Abstract

Background and Objectives

Warfarin and other anticoagulant medications like Coumadin are widely prescribed by physicians to prevent ischemic events. A variety of factors such as sex, age and weight can affect warfarin dosage requirements. A clinical effect of warfarin depends on highly polymorphic drug-metabolizing (CYP2C9) enzymes. The objective of this study was to investigate the impact of CYP2C9*2, CYP2C9*3 polymorphisms on the variability of warfarin dosage requirements in Iranian population that were under warfarin therapy for different reasons.

Materials and Methods

The study included 100 patients with the mean age of 61.3 years. The restriction fragment length polymorphism method was used to identify polymorphisms of CYP2C9 (*1, *2, *3) in Iranian patients with ischemic heart disease in Peyvand Laboratory.

Results

Two-thirds (68.42%) of the patients had the wild-type (WT) CYP2C9*1*1 genotype 10.53%, 18.95%, and 2.1% of the patients had CYP2C9 *1*2, *1*3, and *2*3 genotype, respectively. WT CYP2C9*1*1 genotype was associated with a higher daily warfarin dosage (4.58 ± 1.57 mg/day  p= 0.02) as compared to other CYP2C9 genotypes.

Conclusions

The Iranian study sample is characterized by high frequency *1*1 genotypes that determine a higher warfarin-loading dose. Analysis of CYP2C9 gene variants allows the prediction of warfarin dosage. These results can be used to individualize treatment with warfarin in Iranian patients.