Warfarin pharmacogenetics: development of a dosing algorithm for Omani patients

被引:0
作者
Anil Pathare
Murtadha Al Khabori
Salam Alkindi
Shoaib Al Zadjali
Rhea Misquith
Hammad Khan
Claudine Lapoumeroulie
Andras Paldi
Rajagopal Krishnamoorthy
机构
[1] Sultan Qaboos University Hospital,Department of Haematology
[2] College of Medicine and Health Sciences,undefined
[3] SQU,undefined
[4] INSERM,undefined
[5] UMR_S 763,undefined
[6] Hopital Robert Debre,undefined
[7] Inserm,undefined
[8] U951,undefined
[9] Ecole Pratique des Hautes Etudes,undefined
[10] UMRS_951,undefined
[11] Genethon,undefined
来源
Journal of Human Genetics | 2012年 / 57卷
关键词
admixture; resistance; sensitive; Warfarin;
D O I
暂无
中图分类号
学科分类号
摘要
The objective of our present study was to develop a warfarin dosing algorithm for the Omani patients, as performances of warfarin dosing algorithms vary across populations with impact on the daily maintenance dose. We studied the functional polymorphisms of CYP2C9, CYP4F2 and VKORC1 genes to evaluate their impact on the warfarin maintenance dose in an admixed Omani patient cohort with Caucasian, African and Asian ancestries. We observed a 64-fold inter-patient variability for warfarin to achieve stable international normalized ratio in these patients. Univariate analysis revealed that age, gender, weight, atrial fibrillation, deep vein thrombosis/pulmonary embolism and variant genotypes of CYP2C9 and VKORC1 loci were significantly associated with warfarin dose in the studied patient population. However, multiple regression model showed that only the atrial fibrillation, and homozygous CYP2C9 variant genotypes (*2/*3 and *3/*3) and VKORC1 GA and AA genotypes remained significant. A multivariate model, which included demographic, clinical and pharmacogenetic variables together explained 63% of the overall inter-patient variability in warfarin dose requirement in this microgeographically defined, ethnically admixed Omani patient cohort on warfarin. This locally developed model performed much better than the International Warfarin Pharmacogenetics Consortium (IWPC) model as the latter could only explain 34% of the inter-patient variability in Omani patients. VKORC1 3673G>A polymorphism emerged as the single most important predictor of warfarin dose variability, even in this admixed population (partial R2=0.45).
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页码:665 / 669
页数:4
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