The impact of , , and polymorphisms on warfarin dose requirement in Saudi patients.

BACKGROUND

Limited data are available on factors that affect warfarin dose requirement in Saudi patients. Saudis are among the underrepresented ethnic groups in warfarin pharmacogenetics research. The present study investigated the frequency of and, (G1347A) and -1639G>A genotypes and their impact on warfarin dose requirement in a cohort of Saudi patients requiring anticoagulation therapy.

METHODS

193 patients on chronic warfarin therapy and with stable anticoagulation took part in the study. Genotyping for 1639G>A, G1347A, 430C>T and 1075A>C were performed using TaqMan genotyping assays. Analysis of variance was carried out to determine the association between , and genotype and warfarin dose requirement in two groups based on target INR range. Backward linear regression analysis identified genetic and clinical factors influencing doe requirements.

RESULTS

Patients with and polymorphisms required significantly lower warfarin doses compared to wild-type patients. Carriers of two mutant alleles required lower doses than those with one mutant allele. In contrast, polymorphisms did not influence warfarin dose. Age and genetic variants in and were negatively correlated with dose requirements, while body surface area (BSA) was positively correlated.

CONCLUSION

Saudi patients with polymorphisms in and required lower warfarin doses than those with the wild-type allele. polymorphism had no effect on warfarin dose requirement. Integrating patient clinical factors, including age and BSA, and genetic polymorphisms in and provides the best estimation of factors contributing to warfarin dose in the Saudi patient population.