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Genetic Polymorphisms of CYP2C9: Comparison of Prevalence in the Lebanese Population with Other Populations

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DOI: 10.4236/pp.2011.22011    5,697 Downloads   12,973 Views   Citations

ABSTRACT

Background: There is little knowledge about genotyping of cytochrome P450s in the Middle East, and there has not been any report on the genotype of CYP 2C9 allelic variants in Lebanese population. Aims and objectives: The purpose of the study was to determine and compare the frequencies of the cytochrome P450 CYP2C9 variants in the Lebanese population with the frequencies in other ethnic populations. Methods: CYP2C9 genotypes were determined in a total of 146 samples of unrelated, healthy Lebanese individuals residing in different areas in Lebanon. Following DNA extraction from buccal cells and polymerase chain reaction, genotyping was performed by Pyrosequencing method. CYP2C9 genotypes results were compared to other populations; i.e., Middle Easterns, Europeans, Asians, and African Americans. Results and discussion: The frequencies of the CYP2C29*2, CYP2C9*3, and CYP2C9*4 alleles were 11.305%, 11.645%, and 1.025% respectively. No CYP2C9*5 allele variants were found among the Lebanese study sample. Vol- unteers could be divided into three CYP2C9 genotype groups: subjects (76.71%) with no mutated alleles (CYP 2C9*1*1; homozygous extensive metabolizers, EM), 21.23% with one mutated allele (CYP 2C9*1*2, *1*3, *1*4, and *1*5; heterozygous intermediate metabolizers IM), and 2.06% with two mutated alleles, homozygous variants as poor metabolizers, PM). The comparative analysis using genotype groups of different populations showed differences among Leba- nese and other Caucasians. Conclusion: This is the first report from Lebanon on CYP2C9 variants; it highlights a higher frequency of CYP2C9 extensive metabolizers compared to other populations including Caucasians. The results serve as a database on CYP 2C9 polymorphisms and baseline clinical data for dosing and avoiding adverse drug reac- tions of drugs metabolised by CYP2C9 in Lebanese patients.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Y. Saab and T. Langaee, "Genetic Polymorphisms of CYP2C9: Comparison of Prevalence in the Lebanese Population with Other Populations," Pharmacology & Pharmacy, Vol. 2 No. 2, 2011, pp. 88-93. doi: 10.4236/pp.2011.22011.

References

[1] C. R. Lee, J. A. Goldstein and J. A. Pieper, “Cytochrome P450 2C9 Polymorphisms: A Comprehensive Review of the in-vitro and Human Datam,” Pharmacogenetics, Vol. 12, No. 3, 2002, pp. 251-263. doi:10.1097/00008571-200204000-00010
[2] D. Si, Y. Guo, Y. Zhang, L. Yang, H. Zhou and D. Zhong, “Identification of a Novel Variant CYP2C9 Allele in Chinese,” Pharmacogenetics, Vol. 14, No. 7, 2004, pp. 465-469. doi:10.1097/01.fpc.0000114749.08559.e4
[3] K. Maekawa, N. Harakawa, E. Sugiyama, M. Tohkin, S. R. Kim, N. Kaniwa, et al., “Substrate-dependent Functional Alterations of Seven CYP2C9 Variants Found in Japanese Subjects,” Drug Metabolism and Disposition, Vol. 37, No. 9, 2009, pp. 1895-903. doi:10.1124/dmd.109.027003
[4] G. P. Aithal, C. P. Day, P. J. Kesteven and A. K. Daly, “Association of Polymorphisms in the Cytochrome P450 CYP2C9 with Warfarin Dose Requirement and Risk of Bleeding Complications,” Lancet, Vol. 353, No. 9154, 1999, pp. 717-719. doi:10.1016/S0140-6736(98)04474-2
[5] U. I. Schwarz, “Clinical Relevance of Genetic Polymorphisms in the Human CYP2C9 Gene,” European Journal of Clinical Investigation, Vol. 33, Suppl. 2, 2003, pp. 23-30. doi:10.1046/j.1365-2362.33.s2.6.x
[6] Y. R. Yoon, J. H. Shon, M. K. Kim, Y. C. Lim, H. R. Lee, J. Y. Park, et al., “Frequency of Cytochrome P450 2C9 Mutant Alleles in a Korean Population,” British Journalof Clinical Pharmacology, Vol. 51, No. 3, 2001, pp. 277- 280.
[7] Y. B. Saab, W. Kabbara, C. Chbib and P. R. Gard, “Buccal Cell DNA Extraction: Yield, Purity, and Cost: A Comparison of Two Methods,” Genetic Testing, Vol. 11, No. 4, 2007, pp. 413-416. doi:10.1089/gte.2007.0044
[8] T. Langaee and M. Ronaghi, “Genetic Variation Analyses by Pyrosequencing,” Mutatiton Research, Vol. 573, No. 1-2, 2005 pp. 96-102. doi:10.1016/j.mrfmmm.2004.07.023
[9] C. Aquilante, M. Lobmeyer, T. Langaee and J. Johnson, “Comparison of Cytochrome P450 2C9 Genotyping Methods and Implications for the Clinical Laboratory,” Pharmacotherapy, Vol. 24, No. 6, 2004, pp. 720-726. doi:10.1592/phco.24.8.720.36074
[10] M. W. Hruska, R. F. Frye and T. Y. Langaee, “Pyrosequencing Method for Genotyping Cytochrome P450 CYP2C8 and CYP2C9 Enzymes,” Clinical Chemistry, Vol. 50, No. 12, 2004, pp. 2392-2395. doi:10.1373/clinchem.2004.040071
[11] Y. B. Saab, P. R. Gard, M. S. Yeoman, B. G. Mfarrej, H. E. El-Moalem and M. J. Ingram, “Renin Angiotensin-System Gene Polymorphisms and Depression,” Progress in Neuro-Psychopharmacology and Biology & Psychiatry, Vol. 31, No. 5, 2007, pp. 1113-1118.
[12] J. D. Nunnelee, “Review of an Article: The International Warfarin Pharmacogenetics Consortium (2009). Estimation of the Warfarin Dose with Clinical and Pharmacogenetic Data. NEJM 360 (8): 753-64,” Journal of Vascular Nursing, Vol. 27, No. 4, 2009, p. 109. doi:10.1016/j.jvn.2009.09.001
[13] A. R. Redman, “Implications of Cytochrome P450 2C9 Polymorphism on Warfarin Metabolism and Dosing,” Pharmacotherapy, Vol. 21, No. 2, 2001, pp. 235-242. doi:10.1592/phco.21.2.235.34106
[14] M. K. Higashi, D. L. Veenstra, L. M. Kondo, A. K. Wittkowsky, S. L. Srinouanprachanh, F. M. Farin, et al., “Association between CYP2C9 Genetic Variants and Anticoagulation-Related Outcomes during Warfarin Therapy,” Journal of the American Medical Association, Vol. 287, No. 13, 2002, pp. 1690-1698. doi:10.1001/jama.287.13.1690
[15] M. W. Linder, S. Looney and J. E. Adams, N. Johnson, D. Antonino-Green, N. Lacefield, et al., “Warfarin Dose Adjustments Based on CYP2C9 Genetic Polymorphisms,” Journal of Thrombosis Thrombolysis, Vol. 14, No. 3, 2002, pp. 227-232. doi:10.1023/A:1025052827305
[16] C. H. Luo, A. Wang, R. H. Zhu, W. X. Zhang, W. Mo, B. N. Yu, G. L. Chen, D. S. Ou-Yang, X. H. Duan, A. M. Abd El-Aty and H. H. Zhou, “Gender Specific Association of CYP2C9*3 with Hyperlipidaemia in Chinese,” British Journalof Clinical Pharmacology. Vol. 60, No. 6, 2005, pp. 629-631.
[17] S. Csilla, L. Lilla, S. Melinda, I. Takacs, T. Viola, P. Noemi, F. Andras and M. Bela, “Interethnic Differences of CYP2C9 Alleles in Healthy Hungarian and Roma Population Samples: Relationship to Worldwide Allelic Frequencies,” Blood Cells, Molecules, and Diseases, Vol. 43, No. 3, 2009, pp. 239-242.
[18] M. Wadelius, L. Y. Chen, J. D. Lindh, N. Eriksson, M. J. Ghori, S. Bumpstead, et al., “The Largest Prospective Warfarin-Treated Cohort Supports Genetic Forecasting,” Blood, Vol. 113, No. 4, 2009, pp. 784-790. doi:10.1182/blood-2008-04-149070
[19] S. Ozawa, B. Shoket, L. P. McDaniel, Y. M. Tang, C. B. Ambrosone, S. Kostic, et al., “Analyses of Bronchial Bulky DNA Adduct Levels and CYP2C9, GSTP1 and NQO1 Genotypes in a Hungarian Study Population with Pulmonary Diseases,” Carcinogenesis, Vol. 20, No. 6, 1999, pp. 991-995. doi:10.1093/carcin/20.6.991
[20] O. Nihat, C. Nese, T. Burak, O. Songul, U. Huseyin, O. Dilaver, C. Mehmet and C. Figer, “The Impact of CYP2C9 and VKORC1 Genetic Polymorphism and Patient Characteristics upon Warfarin Dose Requirements in an Adult Turkish Population,” Heart Vessels, Vol. 25, No. 2, 2010, pp. 155-162.
[21] N. A. Limdi, G. McGwin, J. A. Goldstein, T. M. Beasley, D. K. Arnett, B. K. Adler, M. F. Baird, R. T. Acton, “Influence of CYP2C9 and VKORC1 1173C/T Genotype on the Risk of Hemorrhagic Complications in African- American and European-American Patients on Warfarin,” Clinical Pharmacology and Therapeutics, Vol. 83, No. 2, 2008, pp. 312-321. doi:10.1038/sj.clpt.6100290
[22] A. Lerena, P. Dorado, F. O’Kirwan, R. Jepson, J. Licinio and M. L. Wong, “Lower Frequency of CYP2C9*2 in Mexican-Americans Compared to Spaniards,” Pharmaco- genomics Journal, Vol. 4, No. 6, 2004, pp. 403-406. doi:10.1038/sj.tpj.6500278
[23] V. Heydy, K. Bravo-Villalta, K. N. Yamamoto, B. Ana and R. H. Yuko Okada, “Genetic Polymorphism of CYP2C9 and CYP2C19 in a Bolivian Population: An In- vestigative and Comparative Study,” British Journalof Clinical Pharmacology, Vol. 61, No. 3, 2005, pp. 179-184.
[24] E. A. Sconce, T. I. Khan, H. A. Wynne, P. Avery, L. Monkhouse, B. P. King, et al., “The Impact of CYP2C9 and VKORC1 Genetic Polymorphism and Patient Characteristics upon Warfarin Dose Requirements: Proposal for a New Dosing Regimen,” Blood, Vol. 106, No. 7, 2005, pp. 2329-2333. doi:10.1182/blood-2005-03-1108
[25] V. Siguret, I. Gouin, J. L. Golmard, S.Geoffroy, J. P. Andreux and E. Pautas, “Cytochrome P450 2C9 Polymorphisms (CYP2C9) and Warfarin Maintenance Dose in elderly Patients,” La revue de médecine interne, Vol. 25, No. 4, 2004, pp. 271-274. doi:10.1016/j.revmed.2003.11.006
[26] M. Moridani, L. Fu, R. Selby, F. Yun, T. Sukovic, B. Wong, et al., “Frequency of CYP2C9 Polymorphisms Affecting Warfarin Metabolism in a Large Anticoagulant Clinic Cohort,” Clinical Biochemistry, Vol. 39, No. 6, 2006, pp. 606-612. doi:10.1016/j.clinbiochem.2006.01.023
[27] M. Tanira, M. A. Al-Mukhaini, A. T. Al-Hinai, K. A. Al Balushi and I. S. Ahmed, “Frequency of CYP2C9 Genotypes among Omani Patients Receiving Warfarin and Its Correlation with Warfarin Dose,” Community Genetics, Vol. 10, No. 1, 2007, pp. 32-37. doi:10.1159/000096279
[28] J. Van der Weide, L. S. Steijns, M. J. Van Weelden and K. de Haan, “The Effect Genetic Polymorphism of Cytochrome P450 CYP2C9 on Phenytoin Dose Requirement,” Pharmacogenetics, Vol. 11, No. 4, 2001, pp. 287-291. doi:10.1097/00008571-200106000-00002
[29] S. N. Pschelina, A. E. Sirotkina, T. V. Taraskina, A. L. Vavilova, A. L. Shwarzman and E. I. Shwartz, “The Frequency of Cyochrome P450 2C9 Genetic Variants in the Russian Population and Their Associations with Individual Sensitivity to Warfarin Therapy,” Thrombosis Research, Vol. 115, No. 3, 2005, pp. 199-203. doi:10.1016/j.thromres.2004.08.020
[30] A. C. Allabi, J. L. Gala, J. P. Desager, M. Heusterspreute and Y. Horsmans, “Genetic Polymorphisms of CYP2C9 and CYP2C19 in the Beninese and Belgian Populations,” British Journal of Clinical Pharmacology, Vol. 56, No. 6, 2003, pp. 653-657. doi:10.1046/j.1365-2125.2003.01937.x
[31] S. A. Scott, L. Edelmann, R. Kornreich, M. Erazo and R. J. Desnick, “CYP2C9, CYP2C19 and CYP2D6 Allele Frequencies in the Ashkenazi Jewish Population,” Pharmacogenomics, Vol. 8, No. 7, 2007, pp. 721-730. doi:10.2217/14622416.8.7.721
[32] H. Samar, H. Masahiro, N. Kaori, E. Mervat, M. Nadia, A. Mohammed and M. Michiano, “Allele and Genotype Frequencies of Polymorphic Cytochromes P 450 (CYP2C9, CYP2C19, CYP2EI) and Dihydropyrimidine Dehydro- genase (DPYD) in the Egyptian Population,” British Journalof Clinical Pharmacology, Vol. 53, No. 6, 2002, pp. 596-603.

  
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