Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지

Single Nucleotide Polymorphism in Cytochrome P450 2E1 among Korean Patients on Warfarin Therapy

  • Han, Dong-Hoon (Dept. of Biochemistry, College of Dentistry) ;
  • Lee, Min-Jeon (Dept. of Biomedical Science, Kyung Hee University) ;
  • Kim, Jeong-Hee (Dept. of Biochemistry, College of Dentistry) ;
  • Lee, Suk-Hyang (Graduate School of Clinical Pharmacy, Sookmyung Womens University)
  • Published : 2006.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

This study was designed to assess the distribution of cytochrome P450 2E1 (CYP2E1) polymorphism among Korean patients on warfarin therapy. CYP2E1 polymorphism was analyzed at 5' flanking region of CYP2E1 gene using restriction fragment length polymorphism method. Patient characteristics including the measured internal normalized ratio (INR) were also evaluated. Based on the warfarin dose and the bleeding cases, the patients were grouped as the regular dose control, the regular dose bleeding, the low dose control, and the low dose bleeding. Total 96 patients were evaluated for both Pst I and Rsa I loci of the CYP2E1 gene and the results showed that both loci were tightly linked. Thirty-three patients(34.4%) were heterozygotes and 4 patients(4.2%) were homozygote. There was no significant difference in patient characteristics in the dose and bleeding case groups. CYP2E1 polymorphism showed a little difference among the groups but was not statistically significant, however, lower INR value was observed in homozygote genotype groups. It was also revealed that genotype allele frequencies of CYP2E1 in Korean was close to other Asian groups but was significantly different from other Caucasian and African-American populations.

Keywords

References

  1. Aithal, G. P., Day, C. P., Kesteven, P. J. L. and Daly, A. K. (1999). Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 353, 717-719 https://doi.org/10.1016/S0140-6736(98)04474-2
  2. Chao, Y.-C., Young, T.-H., Chang, W.-K., Tang, H.-S. and Hsu, C.-T. (1995). An investigation of whether polymorphisms of cytochrome P4502El are genetic markers of susceptibility to alcoholic end-stage organ damage in a Chinese population. Hepatology 22, 1409-1414
  3. Coon, M. J. (2003). Multiple oxidants and mutiple mechanisms in cytochrome P450 catalysis. Biochem. Biophys. Res. Commun. 312, 163-189 https://doi.org/10.1016/j.bbrc.2003.10.084
  4. Furuya, H., Fernandez-Salguero, P., Gregory, W., Taber, H., Steward, A., Gonzalez, F. J. and Idle, J. R. (1995). Genetic polymorphism of CYP2C9 and its effect on warfarin maintenance dose requirement in patients undergoing anticoagulation therapy. Pharmacogenetics 5, 389-392 https://doi.org/10.1097/00008571-199512000-00008
  5. Griese, E. -U., Ilett, K. F., Kitteringham, N. R., Eichelbaum, M., Powell, H., Spargo, R. M., LeSouef, P. N., Musk, A. W. and Minchin, R. F. (2001). Allele and genotype frequencies of polymorphic cytochromes P450 2D6, 2C19 and 2E1 in Aborigines from Western Australia. Pharmacogenetics 11, 69-76 https://doi.org/10.1097/00008571-200102000-00008
  6. Hamdy, S. I., Hiratsuka, M., Narahara, K., El-Enany, M., Moursi, N., Ahmed, M. S. -E. and Mizugaki, M. (2002). Allele and genotype frequencies of polymorphic cytochrome P450 (CYP2C9, CYP2C19, CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian population. Br. J. Clin. Pharmacol. 53, 596-603 https://doi.org/10.1046/j.1365-2125.2002.01604.x
  7. Hayashi, S., Watanabe, J. and Kawajiri, K. (1991). Genetic polymorphisms in the 5' -flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J. Biochem. 110, 559-565 https://doi.org/10.1093/oxfordjournals.jbchem.a123619
  8. Ingelman-Sundberg, M. (2004) Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms. Naunyn-Schmiedeberg's Arch. Pharmacol. 369, 89-104 https://doi.org/10.1007/s00210-003-0819-z
  9. Itoh, K., Inoue, K., Nakao, H., Yanagiwara, S., Tada, H. and Suzuki, T. (2000) Polymerase chain reaction-single stranded conformation polymorphism based determination of two major genetic defects responsible for a phenotypic polymorphism of cytochrome P450 (CYP) 2c19 in the Japanese population. Anal. Biochem. 284, 160-162 https://doi.org/10.1006/abio.2000.4671
  10. Iwahashi, K., Nakamura, K., Suwaki, H., Matsuo, Y. and Ichikawa, Y. (1994). Relationship between genetic polymorphism of CYP2E1 and ALDH2, and possible susceptibility to alcoholism. Alcohol Alcoholism 29, 639-642
  11. Kim, R. B., O'Shea, D. Wilkinson, G. R. (1995). Interindividual variability of chlorzoxazone 6-hydroxylatin in men and women and its relationship to CYP2E1 genetic polymorphisms. Clin. Pharmacol. Ther. 57, 645-655 https://doi.org/10.1016/0009-9236(95)90227-9
  12. Lee, K. -H., Kwak, B. -Y., Kim, J. -H., Yoo, S. -K., Yeom, S. -K. and Jeong, H. -S. (1997). Genetic polymorphism of cytochrome P 450El and Mitochondrial aldehyde dehydrogenase in a korean population. Alcohol. Clin. Exp. Res. 21, 953-956 https://doi.org/10.1111/j.1530-0277.1997.tb04236.x
  13. Lee, S., Kim, J. M., Chung, C. S., Cho, K. J. and Kim, J. H. (2003). Polymorphism in CYP2C9 as a non-critical factor of warfarin dosage adjustment in Korean patients. Arch. Pharm. Res. 26, 967-972 https://doi.org/10.1007/BF02980207
  14. McCarver, D. G., Byun, R., Hines, R. N., Hichme, M. and Wegenek, W. (1998). A genetic polymorphism in the regulatory sequences of human CYP2El: Assoctiation with increased chlorzoxazone hydroxylation in the presence of obesity and ethanol intake. Toxicol. Appl. Pharmacol. 152, 276-281 https://doi.org/10.1006/taap.1998.8532
  15. Persson, I., Johnasson, I., Bergling, H., Dahl, M. -L., Seidegard, J., Rylander, R., Rannug, A., Hogberg, J. and Sundberg, M. I. (1993). FEBS Lett. 319, 207-211 https://doi.org/10.1016/0014-5793(93)80547-8
  16. Scordo, M. G., Pengo, V., Spina, E., Dahl, M. L., Gusella, M. and Padrini, R. (2002). Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance. Clin. Pharmacol. Ther. 72, 702-710 https://doi.org/10.1067/mcp.2002.129321
  17. Tanaka, E. (1999). Genetic polymorphism of drug metabolizing enzymes in humans. J. Clin. Pharm. Ther. 24, 323-329 https://doi.org/10.1046/j.1365-2710.1999.00236.x
  18. Terelius, Y., Norsten-Hoog, C., Cronholm, T. and Ingeman-Sundberg, M. (1991). Acetaldehyde as a substrate for ethanol-inducible cytochrome P450 (CYP2E1). Biochem. Biophys. Res. Commun. 179, 689-694 https://doi.org/10.1016/0006-291X(91)91427-E
  19. Ueno, Y., Adachi, J., Imamichi, H., Nishimura, A. and Tatsuno, Y (1996). Effect of the cytochrome P-450IIE1 genotype on ethanol elimination rate in alcoholics and control subjects. Alcohol. Clin. Exp. Res. 20, 17A-21A
  20. Umeno, M., McBride, O. W., Yang, C. S., Gelboin, H. V. and Gonzalez, F. J. (1988). Human ethanol-inducible P450IIE1: Complete gene sequence, promoter characterization, chromosome mapping and eDNA-directed expression. Biochemistry 27, 9006-9013 https://doi.org/10.1021/bi00425a019
  21. Vidal, F., Lorenzo, A., Auguet, T., Olona, M., Broch, M., Gutierrez, C., Aguilar, C., Estupifia, P., Santos, M. and Richart, C. (2004). Genetic polymorphisms of $ADH_2$, $ADH_3$, $CYP_{450}2E1$ Dra-I and Pst-I, and $ALDH_2$ in Spanish man: lack of association with alcoholism and alcoholic liver disease. J. Hepatol. 41, 744-750 https://doi.org/10.1016/j.jhep.2003.06.003
  22. Watanabe, J., Hayashi, S. Kawajiri, K. (1994). Different regulation and expression of the human CYP2El gene due to the RsaI polymorphism in the 5'-flanking region. J. Biochem. 116, 321-326 https://doi.org/10.1093/oxfordjournals.jbchem.a124526