Analysis of CYP2C9 polymorphisms (*2 and *3) in warfarin therapy patients in Pakistan. Association of CYP2C9 polymorphisms (*2 and*3) with warfarin dose, age, PT and INR.

ABSTRACT

Warfarin is a widely used anticoagulant characterized by having a narrow therapeutic index and exhibiting a wide range of inter-individual and inter-ethnic variation. Single nucleotide polymorphisms in hepatic VKORC1 and CYP2C9 genes causes decreased and increased metabolism of warfarin respectively. The objective of this study was to evaluate the allele frequency of CYP2C9 polymorphic variants *2 and *3 and the association of these allelic variants with PT/INR and daily/weekly dose of warfarin. Seventy-four patients with heart valve replacement were selected. Patients taking low warfarin dose (4.90-17.50 mg weekly) for at least last 3 months and had a stable INR in the range of 2-3 were included in this study. CYP2C9 polymorphism was analyzed by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) technique. Among 74 patients, 9 (12.1 %) showed to have *2 allele, whereas 11 (14.1 %) had *3 allele. Genotype frequencies of wild and variant alleles were, 54.1, 17.6, 21.6 and 6.8 % for *1/*1, *1/*2, *1/*3 and *2/*3 respectively. None of the patient was homozygous for *2 and *3. Statistical analysis showed that low warfarin dose (weekly) is significantly associated with *1/*2 and *1/*3 genotypes (p value ≥ 0.001), whereas PT/INR showed no significant association with the any genotypes of CYP2C9. Our study suggest that polymorphic variants of CYP2C9 (*2 and *3) might influence warfarin dose requirements and associated with the low dose of warfarin in patients.