Biology:CYP2C9*13

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Cytochrome P450 2C9 (CYP2C9), a member of the CYP2C enzyme subfamily, ranks amongst the most important drug metabolizing enzymes in humans. Human CYP2C9 has been shown to exhibit genetic polymorphism. In addition to the wild-type protein CYP2C9*1, at least 30 single nucleotide polymorphisms (SNPs) have been reported within the coding region of the CYP2C9 gene producing the variant allozymes. CYP2C9*13 is one of them. It involves a T-to-C transversion at nucleotide position 269 causing a mutation at codon 90, which results in a Leu->Pro substitution. Frequency analysis indicated approximately 2% of the Chinese population carry the allele.[1][2]

CYP2C9*13 was found in Japanese and Korean,[3][4][5] too. CYP2C9*13 allele frequencies in East Asian populations is summarized in Table S of this paper.[6]

CYP2C9*13 allele was correlated with reduced plasma clearance of drugs that are substrates for CYP2C9.[7][8][9][10][11][12]

References

  1. ↑ Dayong, Si; Yingjie, Guo; Yifan, Zhang; Lei, Yang; Zhou; Dafang, Zhong (Jul 2004). "Identification of a novel variant CYP2C9 allele in Chinese". Pharmacogenetics 14 (7): 465–9. doi:10.1097/01.fpc.0000114749.08559.e4. PMID 15226678. http://p4502c.googlepages.com/my.pdf. 
  2. ↑ Yifan, Zhang; Dafang, Zhong; Dayong, Si; Yingjie, Guo; Xiaoyan, Chen; Hui, Zhou (Jan 2005). "Lornoxicam pharmacokinetics in relation to cytochrome P450 2C9 genotype". British Journal of Clinical Pharmacology 59 (1): 14–7. doi:10.1111/j.1365-2125.2005.02223.x. PMID 15606435. PMC 1884973. http://p4502c.googlepages.com/bcp.pdf. 
  3. ↑ Bae, JW; Kim, HK; Kim, JH; Yang, SI; Kim, MJ; Jang, CG; Park, YS; Lee, SY (Oct 2005). "Allele and genotype frequencies of CYP2C9 in a Korean population". Br J Clin Pharmacol 60 (4): 418–22. doi:10.1111/j.1365-2125.2005.02448.x. PMID 16187974. 
  4. ↑ Tong, YIN; Keiko, MAEKAWA; Kei, KAMIDE; Yoshiro, SAITO; Hironori, HANADA; Kotaro, MIYASHITA; Yoshihiro, KOKUBO; Yasuhisa, AKAIWA et al. (2008). "Genetic Variations of CYP2C9 in 724 Japanese Individuals and Their Impact on the Antihypertensive Effects of Losartan". Hypertens Res 31 (8): 1149–57. doi:10.1291/hypres.31.1549. PMID 18971529. 
  5. ↑ Lee, H. W. (2011). "Frequency of CYP2C9 variant alleles, including CYP2C9*13 in a Korean population and effect on glimepiride pharmacokinetics". J Clin Pharm Ther. 37: 105–111. doi:10.1111/j.1365-2710.2010.01238.x. PMID 21208246. 
  6. ↑ Si, Dayong; Wang, Juan; Zhang, Yifan; Zhong, Dafang; Zhou, Hui (2012). "Distribution of CYP2C9*13 allele in the Chinese Han and the long-range haplotype containing CYP2C9*13 and CYP2C19*2". Biopharmaceutics & Drug Disposition 33 (6): 342–345. doi:10.1002/bdd.1804. PMID 22886551. 
  7. ↑ Yingjie, Guo; Yifan, Zhang; Ying, Wang; Xiaoyan, Chen; Dayong, Si; Dafang, Zhong; Fawcett, JP; Zhou (Jun 2005). "Role of CYP2C9 and its variants (CYP2C9*3 and CYP2C9*13) in the metabolism of lornoxicam in human". Drug Metab Dispos 33 (6): 749–53. doi:10.1124/dmd.105.003616. PMID 15764711. http://p4502c.googlepages.com/dmd.pdf. 
  8. ↑ Yingjie, Guo; Ying, Wang; Dayong, Si; Fawcett, PJ; Dafang, Zhong; Hui, Zhou (Sep 2005). "Catalytic activities of human cytochrome P450 2C9*1, 2C9*3 and 2C9*13". Xenobiotica 35 (9): 853–861. doi:10.1080/00498250500256367. PMID 16308280. http://p4502c.googlepages.com/Xenobiotica.PDF. [yes|permanent dead link|dead link}}]
  9. ↑ Yihan, Zhou; Qingchuan, Zheng; Li; Yuan, Zhang; Miao, Sun; Chia-Chung, Sun; Dayong, Si; Lei, Cai et al. (2006). "On the human CYP2C9 variant *13 activity reduction: a molecular, dynamics simulation and docking study". Biochimie 88 (10): 1457–1465. doi:10.1016/j.biochi.2006.05.001. PMID 16740353. http://p4502c.googlepages.com/yaoxue.PDF. 
  10. ↑ Li, Z; Wang, G; Wang, LS; Zhang, W; Tan, ZR; Fan, L; Chen, BL; Li, Q et al. (2009). "Effects of the CYP2C9*13 allele on the pharmacokinetics of losartan in healthy male subjects". Xenobiotica 39 (10): 788–793. doi:10.1080/00498250903134435. PMID 19604036. 
  11. ↑ Maekawa, K; Harakawa, N; Sugiyama, E; Tohkin, M; Kim, SR; Kaniwa, N; Katori, N; Hasegawa, R et al. (2009). "Substrate-dependent functional alterations of seven CYP2C9 variants found in Japanese subjects". Drug Metab Dispos 37 (9): 1895–1903. doi:10.1124/dmd.109.027003. PMID 19541829. http://p4502c.googlepages.com/other2.pdf. 
  12. ↑ Bae, JW; Choi, CI; Jang, CG; Lee, SY (Apr 2011). "Effects of CYP2C9*1/*13 on the pharmacokinetics and pharmacodynamics of meloxicam". Br J Clin Pharmacol 71 (4): 550–5. doi:10.1111/j.1365-2125.2010.03853.x. PMID 21395648. 





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