title: Warfarin pharmacogenetics: polymorphisms of the CYP2C9, CYP4F2, and VKORC1 loci in a genetically admixed Omani population.
abstract: This is the first study to evaluate the spectrum and prevalence of dose-predictive genetic polymorphisms of the CYP2C9, CYP4F2 and VKORC1 loci together, in a geographically defined, ethnically admixed healthy adult Omani population sharing common lifestyle/environmental factors. Since the present-day Omani population is the result of an admixture of Caucasian, African and Asian ancestries, we compared the pharmacogenetic profile of these three loci in this population. Interestingly, the Omani pharmacogenetic profile, in terms of allele and genotype distribution, has values that are intermediate between Caucasians and African Americans, the African admixture further substantiated by the presence of the CYP2C9*8 allele. However, limitations and usefulness of such comparisons warrant caution, as the data from pharmacogenetic literature do not always represent bona fide population categories. Furthermore, definition of study population based on microgeographical scale would be more appropriate in pharmacogenetic research rather than the flawed racial, ethnic, or social categorizations since pharmacogenetic variation is clinal, and genetic influences will be further altered by lifestyle and environmental factors.
authors.affiliation: Department of Hematology, Sultan Qaboos University Hospital, Oman.
authors.forename: Anil V
authors.initials: AV
authors.lastname: Pathare
authors.forename: Shoaib
authors.initials: S
authors.lastname: Al Zadjali
authors.forename: Rhea
authors.initials: R
authors.lastname: Misquith
authors.forename: Salam S
authors.initials: SS
authors.lastname: Alkindi
authors.forename: Vinodh
authors.initials: V
authors.lastname: Panjwani
authors.forename: Claudine
authors.initials: C
authors.lastname: Lapoumeroulie
authors.forename: Sahaya
authors.initials: S
authors.lastname: Pravin
authors.forename: Andras
authors.initials: A
authors.lastname: Paldi
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Krishnamoorthy
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D016009:Chi-Square Distribution; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D000072470:Cytochrome P450 Family 4; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009850:Oman; D011110:Polymorphism, Genetic; D015995:Prevalence; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases