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Lower frequency of CYP2C9*2 in Mexican-Americans compared to Spaniards

The Pharmacogenomics Journal volume 4, pages 403–406 (2004)Cite this article

ABSTRACT

Interethnic differences in cytochrome P450 polymorphism might be responsible, at least in part, for the variations in drug disposition between ethnic groups. Of the various CYP2C9 alleles, CYP2C9*2 and CYP2C9*3 have been reported to have altered catalytic activities compared to the wild-type CYP2C9*1. The present study is aimed at analysing the CYP2C9 polymorphism in a Mexican-American compared with a Spanish population. Differences between the two populations of healthy volunteers, Mexican-Americans (n=98 subjects) and Spaniards (n=102 subjects), regarding the CYP2C9 allele frequencies have been found. CYP2C9 genotypes among the studied Mexican-American population are in equilibrium. The 95% CI were, respectively, 0.81–0.90 for CYP2C9*1 (n=169), 0.05–0.13 for CYP2C9*2 (n=16) and 0.031–0.10 for CYP2C9*3 (n=11). CYP2C9*4, *5 and *6 were found in none of the studied subjects. The frequency of CYP2C9*2 was lower among Mexican-Americans compared to Spaniards (P<0.05). The obtained frequency of CYP2C9 alleles is compatible with the genomic assembly of the constitutive potential ethnic origin of this population, and supports the need of pharmacogenetic studies for optimizing the recommended drug dosages to Mexican-Americans.

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References

  1. Rendic S, Di Carlo FJ . Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev 1997; 29: 413–580.

    Article  CAS  Google Scholar 

  2. Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 1996; 6: 1–42.

    Article  CAS  Google Scholar 

  3. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP . Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994; 270: 414–423.

    CAS  Google Scholar 

  4. Goldstein JA, de Morais SM . Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics 1994; 4: 285–299.

    Article  CAS  Google Scholar 

  5. Miners JO, Birkett DJ . Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 1998; 45: 525–538.

    Article  CAS  Google Scholar 

  6. Goldstein JA . Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br J Clin Pharmacol 2001; 52: 349–355.

    Article  CAS  Google Scholar 

  7. Schwarz UI . Clinical relevance of genetic polymorphisms in the human CYP2C9 gene. Eur J Clin Invest 2003; 33 (Suppl 2): 23–30.

    Article  CAS  Google Scholar 

  8. Lee CR, Goldstein JA, Pieper JA . Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. Pharmacogenetics 2002; 12: 251–263.

    Article  CAS  Google Scholar 

  9. Xie HG, Prasad HC, Kim RB, Stein CM . CYP2C9 allelic variants: ethnic distribution and functional significance. Adv Drug Deliv Rev 2002; 54: 1257–1270.

    Article  CAS  Google Scholar 

  10. Dorado P, Berecz R, Norberto MJ, Yasar U, Dahl ML, LLerena A . CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers. Eur J Clin Pharmacol 2003; 59: 221–225.

    Article  CAS  Google Scholar 

  11. Xie HG, Prasad H, Landau R, Kim RB, Cai WM, Ieiri I et al. Frequency of the defective CYP2C9 variant alleles in different ethnic groups. Clin Pharmacol Ther 2002; 71: P102.

    Google Scholar 

  12. Machorro-Lazo MV, Flores-Martínez SE, García-Zapién AG, Mújica-López KI, Morán-Moguel MC, Sánchez-Corona J . Genetic frequency of the variant CYP2C9*2 in Western Mexican Mestizos. HGM 2003; Posters Abstracts, Cancún 2003. (http://hgm2003.hgu.mrc.ac.uk).

  13. Yasar Ü, Forslund-Bergengren C, Tybring G, Dorado P, LLerena A, Sjoqvist F et al. Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin Pharmacol Ther 2002; 71: 89–98.

    Article  CAS  Google Scholar 

  14. Griskevicius L, Yasar U, Sandberg M, Hidestrand M, Eliasson E, Tybring G et al. Bioactivation of cyclophosphamide: the role of polymorphic CYP2C enzymes. Eur J Clin Pharmacol 2003; 59: 103–109.

    Article  CAS  Google Scholar 

  15. Imai J, Ieiri I, Mamiya K, Miyahara S, Furuumi H, Nanba E et al. Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese epileptic patients: genetic analysis of the CYP2C9 locus. Pharmacogenetics 2000; 10: 85–89.

    Article  CAS  Google Scholar 

  16. Kidd RS, Curry TB, Gallagher S, Edeki T, Blaisdell J, Goldstein JA . Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Pharmacogenetics 2001; 11: 803–808.

    Article  CAS  Google Scholar 

  17. Yasar U, Aklillu E, Canaparo R, Sandberg M, Sayi J, Roh HK et al. Analysis of CYP2C9*5 in Caucasian, Oriental and black-African populations. Eur J Clin Pharmacol 2002; 58: 555–558.

    Article  CAS  Google Scholar 

  18. Stubbins MJ, Harries LW, Smith G, Tarbit MH, Wolf CR . Genetic analysis of the human cytochrome P-450 CYP2C9 locus. Pharmacogenetics 1996; 6: 429–439.

    Article  CAS  Google Scholar 

  19. Scordo MG, Aklillu E, Yasar Ü, Dahl M-L, Spina E, Ingelman-Sundberg M . Genetic polymorphism of cytochrome P-450 2C9 in a Caucasian and a Black-African population. Br J Clin Pharmacol 2001; 52: 447–451.

    Article  CAS  Google Scholar 

  20. Yasar Ü, Eliasson E, Dahl ML, Johansson I, Ingelman-Sundberg M, Sjöqvist F . Validation of methods for CYP2C9 genotyping: frequencies of mutant alleles in a Swedish population. Biochem Biophys Res Commun 1999; 254: 628–631, Erratum in: Biochem Biophys Res Commun 1999; 258: 227.

    Article  CAS  Google Scholar 

  21. Dickmann LJ, Rettie AE, Kneller MB, Kim RB, Wood AJ, Stein CM et al. Identification and functional characterization of a new CYP2C9 variant (CYP2C9*5) expressed among African Americans. Mol Pharmacol 2001; 60: 382–387.

    Article  CAS  Google Scholar 

  22. Sullivan-Klose TH, Ghanayem BI, Bell DA, Zhang ZY, Kaminsky LS, Shenfield GM et al. The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics 1996; 6: 341–349.

    Article  CAS  Google Scholar 

  23. Gaedigk A, Casley WL, Tyndale RF, Sellers EM, Jurima-Romet M, Leeder JS . Cytochrome P-4502C9 (CYP2C9) allele frequencies in Canadian Native Indian and Inuit populations. Can J Physiol Pharmacol 2001; 79: 841–847.

    Article  CAS  Google Scholar 

  24. Hamdy SI, Hiratsuka M, Narahara K, El-Enany M, Moursi N, Ahmed MS et al. Allele and genotype frequencies of polymorphic cytochromes P-450 (CYP2C9, CYP2C19, CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian population. Br J Clin Pharmacol 2002; 53: 596–603.

    Article  CAS  Google Scholar 

  25. Peyvandi F, Spreafico M, Karimi M, Zeinali S, Mannucci PM, Bianchi Bonomi A . Allele frequency of CYP2C9 gene polymorphisms in Iran. Thromb Haemost 2002; 88: 874–875.

    Article  CAS  Google Scholar 

  26. Aynacioglu AS, Brockmoller J, Bauer S, Sachse C, Guzelbey P, Ongen Z et al. Frequency of cytochrome P-450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br J Clin Pharmacol 1999; 48: 409–415.

    Article  CAS  Google Scholar 

  27. 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.

    Article  CAS  Google Scholar 

  28. Kimura M, Ieiri I, Mamiya K, Urae A, Higuchi S . Genetic polymorphism of cytochrome P-450s, CYP2C19, and CYP2C9 in a Japanese population. Ther Drug Monitor 1998; 20: 243–247.

    Article  CAS  Google Scholar 

  29. Nasu K, Kubota T, Ishizaki T . Genetic analysis of CYP2C9 polymorphism in a Japanese population. Pharmacogenetics 1997; 7: 405–409.

    Article  CAS  Google Scholar 

  30. Yoon YR, Shon JH, Kim MK, Lim YC, Lee HR, Park JY et al. Frequency of cytochrome P-450 2C9 mutant alleles in a Korean population. Br J Clin Pharmacol 2001; 51: 277–280.

    Article  CAS  Google Scholar 

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Acknowledgements

The present study was supported by the US National Institutes of Health (Grants GM61394, RR017365, RR000865, RR16996, RR017611 and DK063240) and by the Spanish Ministry of Science and Technology (Grant SAF2003-05716), and by an award from the Dana Foundation. The collaboration of MC Cáceres (University of Extremadura) is acknowledged.

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Authors and Affiliations

  1. Center for Pharmacogenomics & Clinical Pharmacology, Neuropsychiatric Institute, David Geffen School of Medicine, University California, Los Angeles, CA, USA

    A LLerena, F O'Kirwan, R Jepson, J Licinio & M-L Wong

  2. Department of Pharmacology and Psychiatry, Faculty of Medicine, University of Extremadura, Badajoz, Spain

    A LLerena & P Dorado

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  1. A LLerena
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Correspondence to M-L Wong.

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LLerena, A., Dorado, P., O'Kirwan, F. et al. Lower frequency of CYP2C9*2 in Mexican-Americans compared to Spaniards. Pharmacogenomics J 4, 403–406 (2004). https://doi.org/10.1038/sj.tpj.6500278

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