Warfarin pharmacogenetics

Development of a dosing algorithm for Omani patients

Anil Pathare, Murtadha Al Khabori, Salam Alkindi, Shoaib Al Zadjali, Rhea Misquith, Hammad Khan, Claudine Lapoumeroulie, Andras Paldi, Rajagopal Krishnamoorthy

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 R 2 0.45).

Original languageEnglish
Pages (from-to)665-669
Number of pages5
JournalJournal of Human Genetics
Volume57
Issue number10
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Pharmacogenetics
Warfarin
Genotype
Atrial Fibrillation
Population
International Normalized Ratio
Pulmonary Embolism
Venous Thrombosis
Demography
Weights and Measures

Keywords

  • admixture
  • CYP2C9
  • CYP4F2
  • resistance
  • sensitive
  • VKORC1
  • Warfarin

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Warfarin pharmacogenetics : Development of a dosing algorithm for Omani patients. / Pathare, Anil; Al Khabori, Murtadha; Alkindi, Salam; Al Zadjali, Shoaib; Misquith, Rhea; Khan, Hammad; Lapoumeroulie, Claudine; Paldi, Andras; Krishnamoorthy, Rajagopal.

In: Journal of Human Genetics, Vol. 57, No. 10, 10.2012, p. 665-669.

Research output: Contribution to journalArticle

Pathare, Anil ; Al Khabori, Murtadha ; Alkindi, Salam ; Al Zadjali, Shoaib ; Misquith, Rhea ; Khan, Hammad ; Lapoumeroulie, Claudine ; Paldi, Andras ; Krishnamoorthy, Rajagopal. / Warfarin pharmacogenetics : Development of a dosing algorithm for Omani patients. In: Journal of Human Genetics. 2012 ; Vol. 57, No. 10. pp. 665-669.
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