%0 Journal Article
%T Genetic factors associated with patient-specific warfarin dose in ethnic Indonesians
%A Ivet M Suriapranata
%A Wen Tjong
%A Tingliang Wang
%A Andi Utama
%A Sunu B Raharjo
%A Yoga Yuniadi
%A Susan SW Tai
%J BMC Medical Genetics
%D 2011
%I BioMed Central
%R 10.1186/1471-2350-12-80
%X Direct sequencing method was used to identify SNPs in CYP2C9, VKORC1, CYP4F2, EPHX1, PROC and GGCX genes in warfarin-treated patients. Multiple linear regressions were performed to model the relationship warfarin daily dose requirement with genetic and non-genetic variables measured and used to develop a novel algorithm for warfarin dosing.From the 40 SNPs analyzed, CYP2C9 rs17847036 and VKORC1 rs9923231 showed significant association with warfarin sensitivity. In our study population, no significant correlation could be detected between CYP2C9*3, CYP2C9C-65 (rs9332127), CYP4F2 rs2108622, GGCX rs12714145, EPHX1 rs4653436 and PROC rs1799809 with warfarin sensitivity.VKORC1 rs9923231 AA and CYP2C9 rs17847036 GG genotypes were associated with low dosage requirements of most patients (2.05 ¡À 0.77 mg/day and 2.09 ¡À 0.70 mg/day, respectively). CYP2C9 and VKORC1 genetic variants as well as non-genetic factors such as age, body weight and body height account for 15.4% of variance in warfarin dose among our study population. Additional analysis of this combination could allow for personalized warfarin treatment in ethnic Indonesians.Warfarin is the most widely used oral anticoagulant in the world. It is usually prescribed for treatment of atrial fibrillation, heart valve prosthesis, recurrent stroke, deep vein thrombosis and pulmonary embolism [1]. Although warfarin is indispensable for treatment of thromboembolism and for prophylaxis of stroke, due to the large inter-individual variation in the requirement for this drug the appropriate dose to each patient is not easily adjustable. An insufficient dose will result in failure to prevent thrombosis, while overdose increases the risk of unexpected bleeding. Pharmacogenetic differences are believed to cause the variation in individual response to warfarin [1,2].Warfarin is primarily metabolized to the 7-hydroxylated form in humans, principally by cytochrome P450 2C9. So far, more than 30 variant alleles in the CYP2C9 gene have
%K Warfarin
%K SNP
%K CYP2C9
%K VKORC1
%K Indonesia
%U http://www.biomedcentral.com/1471-2350/12/80