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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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The effect of CYP1A2 gene polymorphisms on Theophylline metabolism and chronic obstructive pulmonary disease in Turkish patients

  • Uslu, Ahmet (Department of Chest Diseases, Medical Park Hospital) ;
  • Ogus, Candan (Department of Chest Diseases, Faculty of Medicine, Akdeniz University) ;
  • Ozdemir, Tulay (Department of Chest Diseases, Faculty of Medicine, Akdeniz University) ;
  • Bilgen, Turker (Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University) ;
  • Tosun, Ozgur (Department of Biostatistics and Medical Informatics, Faculty of Medicine, Akdeniz University) ;
  • Keser, Ibrahim (Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University)
  • Received : 2010.03.29
  • Accepted : 2010.07.13
  • Published : 2010.08.31
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Abstract

Cytochrome P450 (CYP) 1A2 gene polymorphisms are thought to be involved in the metabolism of theophylline (TP). We aimed to investigate the effect of CYP1A2*1C, CYP1A2*1D, CYP1A2*1E, and CYP1A2*1F polymorphisms of the CYP1A2 on TP metabolism by PCR-RFLP in 100 Turkish patients with chronic obstructive pulmonary disease (COPD) receiving TP. One hundred and one healthy volunteers were included as control group. The genotype frequencies of the CYP1A2*1D and CYP1A2*1F were found to be significantly different in the patients compared to the controls. The "T" allele at -2467 delT and the "C" allele at -163 C > A in the CYP1A2 displayed association with a significantly increased risk for COPD. "T" allele at -2467 delT was also associated with a high risk of disease severity in COPD. In conclusion, our data suggest that genetic alterations in CYP1A2 may play a role both in the pharmacogenetics of TP and in the development of COPD.

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References

  1. http://www.goldcopd.org.
  2. Hanania, N. A. and Donohue, J. F. (2007) Pharmacologic interventions in chronic obstructive pulmonary disease: bronchodilators. Proc. Am. Thorac. Soc. 4, 526-534. https://doi.org/10.1513/pats.200701-016FM
  3. Tjia, J. F., Colbert, J. and Back, D. J. (1996) Theophylline metabolism in human liver microsomes: inhibition studies. J. Pharmacol. Exp. Ther. 276, 912-917.
  4. Derkenne, S., Curran, C. P., Shertzer, H. G., Dalton, T. P., Dragin, N. and Nebert, D. W. (2005) Theophylline pharmacokinetics: comparison of Cyp1a1(-/-) and Cyp1a2(-/-) knockout mice, humanized hCYP1A1_1A2 knock-in mice lacking either the mouse Cyp1a1 or Cyp1a2 gene, and Cyp1(+/+) wild-type mice. Pharmacogenet. Genomics. 15, 503-511. https://doi.org/10.1097/01.fpc.0000167326.00411.50
  5. Potkin, S. G., Bera, R., Gulasekaram, B., Costa, J., Hayes, S., Jin, Y., Richmond, G., Carreon, D., Sitanggan, K. and Gerber, B. (1994) Plasma clozapine concentrations predict clinical response in treatment-resistant schizophrenia. J. Clin. Psychiatry. 55 (Suppl B), 133-136.
  6. Barnes, P. J. (2005) Theophylline in chronic obstructive pulmonary disease: new horizons. Proc. Am. Thorac. Soc. 334-339.
  7. http://www.cypalleles.ki.se/cyp1a2.htm.
  8. Nakajima, M., Yokoi, T., Mizutani, M., Kinoshita, M., Funayama, M. and Kamataki, T. (1999) Genetic polymorphism in the 5'-flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans. J. Biochem. 125, 803-808. https://doi.org/10.1093/oxfordjournals.jbchem.a022352
  9. Sachse, C., Brockmoller, J., Bauer, S. and Roots, I. (1999) Functional significance of a C→A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br. J. Clin. Pharmacol. 47, 445-449. https://doi.org/10.1046/j.1365-2125.1999.00898.x
  10. Aklillu, E., Carrillo, J. A., Makonnen, E., Hellman, K., Pitarque, M., Bertilsson, L. and Ingelman-Sundberg, M. (2003) Genetic polymorphism of CYP1A2 in Ethiopians affecting induction and expression: characterization of novel haplotypes with single-nucleotide polymorphisms in intron 1. Mol. Pharmacol. 64, 659-669. https://doi.org/10.1124/mol.64.3.659
  11. Allorge, D., Chevalier, D., Lo-Guidice, J. M., Cauffiez, C., Suard, F., Baumann, P., Eap, C. B. and Broly, F. (2003) Identification of a novel splice-site mutation in the CYP1A2 gene. Br. J. Clin. Pharmacol. 56, 341-344. https://doi.org/10.1046/j.1365-2125.2003.01858.x
  12. Murayama, N., Soyama, A., Saito, Y., Nakajima, Y., Komamura, K., Ueno, K., Kamakura, S., Kitakaze, M., Kimura, H., Goto, Y., Saitoh, O., Katoh, M., Ohnuma, T., Kawai, M., Sugai, K., Ohtsuki, T., Suzuki, C., Minami, N., Ozawa, S. and Sawada, J. (2004) Six novel nonsynonymous CYP1A2 gene polymorphisms: catalytic activities of the naturally occurring variant enzymes. J. Pharmacol. Exp. Ther. 308, 300-306. https://doi.org/10.1124/jpet.103.055798
  13. Arif, E., Vibhuti, A., Alam, P., Deepak, D., Singh, B., Athar, M. and Pasha, M. A. (2007) Association of CYP2E1 and NAT2 gene polymorphisms with chronic obstructive pulmonary disease. Clin. Chim. Acta. 382, 37-42. https://doi.org/10.1016/j.cca.2007.03.013
  14. Korytina, G. F., Akhmadishina, L. Z., Kochetova, O. V., Zagidullin, Sh. Z. and Viktorova, T. V. (2008) Association of cytochrome P450 genes polymorphisms (CYP1A1 and CYP1A2) with the development of chronic obstructive pulmonary disease in Bashkortostan. Mol. Biol. (Mosk) 42, 32-41.
  15. Jiang, Z., Dragin, N., Jorge-Nebert, L. F., Martin, M. V., Guengerich, F. P., Aklillu, E., Ingelman-Sundberg, M., Hammons, G. J., Lyn-Cook, B. D., Kadlubar, F. F., Saldana, S. N., Sorter, M., Vinks, A. A., Nassr, N., von Richter, O., Jin, L. and Nebert, D. W. (2006) Search for an association between the human CYP1A2 genotype and CYP1A2 metabolic phenotype. Pharmacogenet. Genomics. 16, 359-367. https://doi.org/10.1097/01.fpc.0000204994.99429.46
  16. Ghotbi, R., Christensen, M., Roh, H. K., Ingelman-Sundberg, M., Aklillu, E. and Bertilsson, L. (2007) Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and Koreans. Eur. J. Clin. Pharmacol. 63, 537-546. https://doi.org/10.1007/s00228-007-0288-2
  17. Takata, K., Saruwatari, J., Nakada, N., Nakagawa, M., Fukuda, K., Tanaka, F., Takenaka, S., Mihara, S., Marubayashi, T. and Nakagawa, K. (2006) Phenotype-genotype analysis of CYP1A2 in Japanese patients receiving oral theophylline therapy. Eur. J. Clin. Pharmacol. 62, 23-28. https://doi.org/10.1007/s00228-005-0057-z
  18. Obase, Y., Shimoda, T., Kawano, T., Saeki, S., Tomari, S. Y., Mitsuta-Izaki, K., Matsuse, H., Kinoshita, M. and Kohno, S. (2003) Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma. Clin. Pharmacol. Ther. 73, 468-474. https://doi.org/10.1016/S0009-9236(03)00013-4
  19. Skarke, C., Kirchhof, A., Geisslinger, G. and Lotsch, J. (2005) Rapid genotyping for relevant CYP1A2 alleles by pyrosequencing. Eur. J. Clin Pharmacol. 61, 887-892. https://doi.org/10.1007/s00228-005-0029-3
  20. Soyama, A., Saito, Y., Hanioka, N., Maekawa, K., Komamura, K., Kamakura, S., Kitakaze, M., Tomoike, H., Ueno, K., Goto, Y., Kimura, H., Katoh, M., Sugai, K., Saitoh, O., Kawai, M., Ohnuma, T., Ohtsuki, T., Suzuki, C., Minami, N., Kamatani, N., Ozawa, S. and Sawada, J. (2005) Single nucleotide polymorphisms and haplotypes of CYP1A2 in a Japanese population. Drug. Metab. Pharmacokinet. 20, 24-33. https://doi.org/10.2133/dmpk.20.24
  21. Bernauer, U., Heinrich-Hirsch, B., Tonnies, M., Peter-Matthias, W. and Gundert-Remy, U. (2006) Characterisation of the xenobiotic-metabolizing Cytochrome P450 expression pattern in human lung tissue by immunochemical and activity determination. Toxicol. Lett. 164, 278-288. https://doi.org/10.1016/j.toxlet.2006.01.007
  22. Fukami, T., Nakajima, M., Sakai, H., Katoh, M. and Yokoi, T. (2007) CYP2A13 metabolizes the substrates of human CYP1A2, phenacetin, and theophylline. Drug Metab. Dispos. 35, 335-339.
  23. Zhang, Z. Y. and Kaminsky, L. S. (1995) Characterization of human cytochromes P450 involved in theophylline 8-hydroxylation. Biochem. Pharmacol. 50, 205-211. https://doi.org/10.1016/0006-2952(95)00120-O
  24. Chida, M., Yokoi, T., Fukui, T., Kinoshita, M., Yokota, J. and Kamataki, T. (1999) Detection of three genetic polymorphisms in the 5'-flanking region and intron 1 of human CYP1A2 in the Japanese population. Jpn. J. Cancer. Res. 90, 899-902. https://doi.org/10.1111/j.1349-7006.1999.tb00832.x

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