Objectives: This study was conducted to determine the frequency of CYP2C9 alleles in Omani patients receiving warfarin and to correlate genotyping data with warfarin dosage. The Omani population has Asian and African ethnicities. Methods: CYP2C9 genotypes were determined by the polymerase chain reaction restriction fragment length polymorphism method. Non-parametric Kruskal-Wallis test was used to compare groups of continuous data for significance differences. Results: Genotyping data showed that 12.7 and 5.8% of the samples were heterozygous for the CYP2C9*2 and CYP2C9*3 alleles, respectively. The CYP2C9*2 allele frequency was 0.074 in our population. It was 0.029 for CYP2C9*3. Conclusion: This is the first report on the presence of CYP2C9*2 allele homozygocity in any Asian or African population.

1.
Higashi MK, Veenstra DL, Kondo LM, Wittkowsky AK, Srinouanprachanh SL, Farin FM, Rettie AE: Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 2002;287:1690–1698.
2.
Van der Meer F, Rosendaal F, Vandenbroucke J, Briet E: Bleeding complications in oral anticoagulation therapy. Arch Intern Med 1993;153:1557–1562.
3.
British Committee for Standards in Hematology: Guidelines on oral anticoagulation. Br J Haematol 1998;101:374.
4.
Hylek EM, Go AS, Chang Y, Jensvold NG, Henault LE, Selby JV, Singer DE: Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003;349:1019–1026.
5.
Budavari S (ed): The Merck Index, ed 11. Rahway, Merck, 1989.
6.
Schroedter IC, Williams G: Frequency of cytochrome P450 CYP2C9 alleles in patients undergoing routine coagulation screening in a large tertiary care facility. J Mol Diagn 1999;1:41.
7.
Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. PharmacolTher1997;73:67–74.
8.
Takahashi H, Echizen H: Pharmacogenetics of warfarin elimination and its clinical implications. Clin Pharmacokinet 2001;40:587–603.
9.
Hirsch J, Dalen DE, Anderson D, et al: Oral anticoagulants. Chest 2001;119(suppl 1):8–21.
10.
James AH, Britt RP, Raskino CL, Thompson SG: Factors affecting the maintenance dose of warfarin. J Clin Pathol 1992;45:704–706.
11.
Steward DJ, Haining RJ, Hanne KR: Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Pharmacogenetics 1997;7:361–367.
12.
Retti AE, Korzekwa KR, Kunze KH, Lawrence RF, Eddy AC, et al: Hydroxylation of warfarin by human cDNA-expressed cytochrome P450: a role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Chem Res Toxicol 1992;5:54–59.
13.
Haining R, Hunter A, Veronese M, Targer W, Rettie A: Allelic variants of human cytochrome P450 2C9: baculovirus-mediated expression purification, structural characterization, substrate sterioselectivity and prochiral selectivity of the wild-type and I359L mutant forms. Arch Biochem Biophys 1996;333:447.
14.
Crespi Cl, Miller VP: The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH. Pharmacogenetics 1997;7:203–210.
15.
Takanashi K, Tainaka H, Kobayashi K, Yasumori T, Hosakawa M, Chiba K: CYP2C9 Ile359 and Leu359 variants. Pharmacogenetics 2000;10:95–104.
16.
Imai J, Jeiri I, Mamiya K, Miyahara S, Furuumi H, Naba E, et al: Polymorphism of cytochrome P450 (CYP) 2C9 gene in Japanese epileptic patients: genetic analysis of the CY2C9 locus. Pharmacogenetics 2000;10:85–89.
17.
Xie HG, Prasad HC, Kim RB, Stein CM: CYP2C9 allelic variants: ethnic distribution and functional significance. Adv Drug Deliv Rev 2002;54:1257–1270.
18.
Dickmann LJ, Rettie AE, Kneller MB, Kim RB, Wood AJ, Stein CM, Wilkinson GR, Schwarz UI: Identification and functional characterization of a new CYP2C9 variant (CYP2C9*5) expressed among African Americans. Mol Pharmacol 2001;60:382–387.
19.
Schwarz UI: Clinical relevance of genetic polymorphisms in the human CYP2C9 gene. Eur J Clin Invest 2003;33(suppl 2):23–30.
20.
Aithal GP, Day CP, Kesteven PJ, Daly AK: Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999;353:717–719.
21.
Stubbins MJ, Harries LW, Smith G, Tarbit MH, Wolf CR: Genetic analysis of the Cytochrome P450 CYP2C9 locus. Pharmacogenetics 1996;6:429–439.
22.
Wang SL, Huang J, Lai MD, Tsai JJ: Detection of CYP2C9 polymorphism based on the polymerase chain reaction in Chinese. Pharmacogenetics 1995;5:37–42.
23.
Goldstein JA: CYP2C9 polymorphisms and CYP2C9*2 genotyping primers. Br JClin Pharmacol2002;53:409–410.
24.
Simsek M, Tanira MO, Al-Baloushi KA, Al-Barwani HS, Lawatia KM, Bayoumi RA: A precaution in the detection of heterozygotes by sequencing: comparison of automated DNA sequencing and PCR-restriction fragment length polymorphism methods. Clin Chem 2001;47:134–137.
25.
Taube J, Halsall D, Baglin T: Influence of cytochrome CYP2C9 polymorphisms on warfarin sensitivity and risk of overcoagulation in patients with long term treatment. Blood 2000;96:1816–1819.
26.
Ferrari P: Pharmacogenomics: a new approach to individual therapy of hypertension. Curr Opin Nephrol Hypertens 1998;7:217–222.
27.
Roden DM, George AL: The genetic basis of variability in drug responses. Nat Rev Drug Discov 2002;1:37–44.
28.
Yoon YR, Shon JH ,Kim MK, Lim YC, Lee HR, Park JY, Cha IJ, Shin JG: Frequency of cytochrome P450 mutant alleles in a Korean population. Br J Clin Pharmacol 2001;51:277–280.
29.
Gage BF, Eby C, Milligan PE, Banet GA, Duncan JR, McLeod HL: Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin. Thromb Haemost 2004;91:87–94.
30.
Leung AY, Chow HC, Kwong YL, Lie AK, Fung AT, Chow WH, Yip AS, Liang R: Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patients. Blood2001;98:2584–2587.
31.
Sullivan-Klose TH, Ghanayem BI, Bell DA, Zhang ZY, Kaminsky LS, Shenfield GM, Miners JO, Birkett DJ, Goldstein JA: The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics1996;6:341–349.
32.
Margaglione M, Colaizzo D, D’Andrea G, Brancaccio V, Ciampa A, Grandone E, Di Minno G: Genetic modulation of oral anticoagulation with warfarin. Thromb Haemost 2000;84:775–778.
33.
Takahashi H, Echizen H: Pharmacogenetics of CYP2C9 and interindividual variability in anticoagulant response to warfarin. Pharmacogenomics J 2003;3:202–214.
34.
Scordo MG, Aklillu E, Yasar U, Dahl ML, Spina E, Ingelman-Sundberg M: Genetic polymorphism of cytochrome P450 2C9 in a Caucasian and a black African population. Br J Clin Pharmacol 2001;52:447–450.
35.
Yasar U, Eliasson E, Dahl ML, Johansson I, Ingelman-Sundberg M, Sjoqvist F: Validation of methods for CYP2C9 genotyping: frequencies of mutant alleles in a Swedish population. Biochem Biophys Res Commun 1999;254:628–631.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.