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

Open Journal of Genetics, 2012, 2, 184-189 OJGen /10.4236/ojgen.2012.24024 Published Online December 2012 (http://www.SciRP.org/journal/ojgen/) 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 , 1* 1,2 1 1 1 3 4 3 Andras Paldi , Rajagopal Krishnamoorthy 1 2 3 4 Department of Hematology, Sultan Qaboos University Hospital, Muscat, Oman College of Medicine Health Sciences, Muscat, Oman INSERM, Université Paris Diderot, Paris, France INSERM, Ecole Pratique des Hautes Etudes, Evry, France Email: pathare@.om * Received 28 September 2012; revised 29 October 2012; accepted 16 November 2012 ABSTRACT adjustment depending upon the INR response until the desired stable INR values were obtained on three con- secutive visits. Inter-patient variability in warfarin dose requirement is multifactorial involving clinical, demo- graphic, life style, environmental and genetic factors [1-3]. Studies involving genome-wide scan have consistently shown that the genetic contribution to warfarin dose re- quirement is restricted to three polymorphic loci, namely CYP2C9, CYP4F2 and VKORC1 [4,5]. Polymorphisms in these three loci vary in frequency across populations, [6,7] and consequently, the relative contribution of the CYP2C9, CYP4F2 and VKORC1 genotypes to the esti- mates of warfarin dose will also vary. Hence the propor- tions of individuals at risk for ADRs will differ across population groups. The variant “warfarin sensitive” alleles of CYP2C9 and VKORC1 account for only 10% of the warfa