Combined effect of CYP2C9 and VKORC1 polymorphisms on warfarin maintenance dose in Omani patients

Anil Pathare, Salam Alkindi, Shoaib Al Zadjali, Rhea Misquith, Fauzia Wasim, Tsouria Berbar, Andras Paldi, Rajagopal Krishnamoorthy

Department of Hematology, Sultan Qaboos University Hospital, Muscat, Oman.
INSERM, Ecole Pratique des Hautes Etudes, Evry, France.
INSERM, Université Paris Diderot, Paris, France.

DOI: 10.4236/ojgen.2012.24024                

Abstract

Excepting host genetic factors, other influences on the pharmacokinetic and pharmacodynamic behavior of warfarin are subject to variations during the treatment despite attempts to stabilize the INR. In 214 Omani patients on warfarin therapy, we evaluated the extent of influence of known genetic predictors of warfarin dose variability, namely CYP2C9, CYP4F2 and VKORC1 gene polymorphisms in a genetically heterogeneous patient population. When patients were stratified according to their daily warfarin maintenance dose (to maintain INR between 2 and 3) into “low dose” (sensitive), “medium dose” (intermediate) and “high dose” (resistance) groups, overall, seven patients with three or four mutant alleles fell in the sensitive group and consequently 25% (7 out of 28) of at risk patients for over anticoagulation can be recognized by prospective pharmacogenetic testing in this patient population. Pre-prescription genotyping of these loci prior to therapy initiation will therefore benefit a small fraction of this population.

Keywords

CYP2C9; CYP4F2; VKORC1; Pharmacogenetics; Polymorphism; Omani

Conflicts of Interest

The authors declare no conflicts of interest.

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