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[edit]

  1. ^ Si Dayong, Guo Yingjie, Zhang Yifan, Yang Lei, Zhou Hui*, Zhong Dafang. Identification of a novel variant CYP2C9 allele in Chinese. Pharmacogenetics. 2004 Jul;14(7):465-9.
  2. ^ Zhang Yifan, Zhong Dafang*, Si Dayong, Guo Yingjie, Chen Xiaoyan, Zhou Hui. Lornoxicam pharmacokinetics in relation to cytochrome P450 2C9 genotype. The British Journal of Clinical Pharmacology. 2005 Jan;59(1):14-7.
  3. ^ Allele and genotype frequencies of CYP2C9 in a Korean population. Br J Clin Pharmacol. 2005 Oct;60(4):418-22
  4. ^ Tong YIN, Keiko MAEKAWA, Kei KAMIDE, Yoshiro SAITO, Hironori HANADA, Kotaro MIYASHITA, Yoshihiro KOKUBO, Yasuhisa AKAIWA, Ryoichi OTSUBO, Kazuyuki NAGATSUKA, Toshiho OTSUKI, Takeshi HORIO, Shin TAKIUCHI, Yuhei KAWANO, Kazuo MINEMATSU, Hiroaki NARITOMI, Hitonobu TOMOIKE, Jun-ichi SAWADA, and Toshiyuki MIYATA1), Genetic Variations of CYP2C9 in 724 Japanese Individuals and Their Impact on the Antihypertensive Effects of Losartan, Hypertens Res Vol. 31, No. 8 (2008), 1149-57
  5. ^ J Clin Pharm Ther. 2011 Jan 5. doi:10.1111/j.1365-2710.2010.01238.x. [Epub ahead of print] Frequency of CYP2C9 variant alleles, including CYP2C9*13 in a Korean population and effect on glimepiride pharmacokinetics.
  6. ^ Dayong Si, Juan Wang, Yifan Zhang, Dafang Zhong and Hui Zhou,Distribution of CYP2C9*13 allele in the Chinese Han and the long-range haplotype containing CYP2C9*13 and CYP2C19*2, Biopharmaceutics & Drug Disposition, 33: 342–345 (2012)
  7. ^ Guo Yingjie, Zhang Yifan, Wang Ying, Chen Xiaoyan, Si Dayong, Zhong Dafang, Fawcett JP, Zhou Hui*. Role of CYP2C9 and its variants (CYP2C9*3 and CYP2C9*13) in the metabolism of lornoxicam in human. Drug Metab Dispos. 2005 Jun;33(6):749-53.
  8. ^ Guo Yingjie, Wang Ying, Si Dayong, Fawcett PJ, Zhong Dafang, Zhou Hui*. Catalytic activities of human cytochrome P450 2C9*1, 2C9*3 and 2C9*13. Xenobiotica 2005 Sep 1;35(9):853-861.
  9. ^ Zhou Yihan; Zheng Qingchuan; Li Zesheng*; Zhang Yuan; Sun Miao; Sun Chia-Chung; Si Dayong; Cai Lei; Guo Yingjie; Zhou Hui*, On the human CYP2C9 variant *13 activity reduction: a molecular, dynamics simulation and docking study, Biochimie, 2006 Volume 88, Issue 10, :1457-1465.
  10. ^ Li Z, Wang G, Wang LS, Zhang W, Tan ZR, Fan L, Chen BL, Li Q, Liu J, Tu JH, Hu DL, Liu ZQ, Zhou HH. Effects of the CYP2C9*13 allele on the pharmacokinetics of losartan in healthy male subjects.Xenobiotica. 2009 Jul 15. [Epub ahead of print]
  11. ^ Maekawa K, Harakawa N, Sugiyama E, Tohkin M, Kim SR, Kaniwa N, Katori N, Hasegawa R, Yasuda K, Kamide K, Miyata T, Saito Y, Sawada JI. Substrate-dependent functional alterations of seven CYP2C9 variants found in Japanese subjects. Drug Metab Dispos. 2009 Jun 18.
  12. ^ Br J Clin Pharmacol. 2011 Apr;71(4):550-5. doi:10.1111/j.1365-2125.2010.03853.x. Effects of CYP2C9*1/*13 on the pharmacokinetics and pharmacodynamics of meloxicam. Bae JW, Choi CI, Jang CG, Lee SY.