Dosing for Warfarin based on CYP 2C9 and VKROC1 patients’ genotypes

Yolande Saab1, Taimour Langaee2

1Lebanese American University, Byblos, Lebanon, 2University of Florida College of Pharmacy, Florida, USA

Warfarin, a commonly prescribed efficacious oral anticoagulant, exhibits large interindividual and interethnic differences in the dose required for its anticoagulant effect. CYP 2C9 and VKORC1 gene polymorphisms have been identified and associated with an increased risk of warfarin over anticoagulation and bleeding events. Evidence suggests different CYP 2C9 and VKORC1 genotypes can be used prospectively to develop warfarin-dosing strategies to avoid the morbidity associated with over anticoagulation. Warfarin starting and maintenance dose adjustment have been determined in several populations; however, Lebanese were not included. Thus the aim of the study was to determine warfarin dosing based on CYP 2C9 (*2 *3*4*5) and VKORC1 functional polymorphisms in the Lebanese population.

DNA swab samples were collected from 146 voluntarily participants. Genotype analysis for the CYP 2C9*2*3*4*5 and VKORC1 alleles was performed by means of PCR analysis, and Pyrosequencer.

Results show that frequencies of CYP2C9 allelic variants among the Lebanese were very high, confirming the higher frequency of CYP 2C9 extensive metabolizers in the Middle East Mediterranean area compared to Southern and Northern Europe, and North America (Table 1). As for VKORC1, CC, TT, and CT genotype frequencies were 36.63%, 23.76% and 39.61% respectively.

In conclusion we recommend clinical trial studies determining optimal drug dosing include samples of diverse populations from the Middle East area.