Genetic polymorphism of cynomolgus and rhesus macaque CYP2C9

Drug Metabolism and Pharmacokinetics
Yasuhiro UnoHiroshi Yamazaki

Abstract

Cynomolgus and rhesus macaques are non-human primate species widely used in drug metabolism studies. Cynomolgus CYP2C9 (formerly known as CYP2C43) is predominantly expressed in liver and encodes a drug-metabolizing enzyme that metabolizes human CYP2C substrates such as S-mephenytoin and progesterone. In addition, cynomolgus CYP2C9 also metabolizes caffeine, resulting in the formation of the metabolite that is not generated efficiently in humans. Genetic variants of human CYP2C genes account for the inter-individual variability in drug metabolism: however, CYP2C9 variants have not been found in macaques. To see if CYP2C9 is polymorphic in macaques, in this study, CYP2C9 was re-sequenced in 78 cynomolgus and 36 rhesus macaques. A total of 27 non-synonymous variants were found, among which 4 were located in substrate recognition sites, the domain important for protein function. Thirteen and seven variants were unique to cynomolgus and rhesus macaques, respectively. This study revealed the polymorphic nature of cynomolgus and rhesus CYP2C9, similar to human CYP2C genes, by identification of numerous genetic variants including non-synonymous variants.

References

Nov 16, 2007·Pharmacology & Therapeutics·Magnus Ingelman-SundbergCristina Rodriguez-Antona
Oct 1, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yasuhiro UnoRyoichi Nagata
Nov 17, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yasuhiro UnoHiroshi Yamazaki
Feb 10, 2011·Drug Metabolism Reviews·Yasuhiro UnoDavid R Nelson
Nov 30, 2011·Drug Metabolism and Pharmacokinetics·Shotaro UeharaYasuhiro Uno
May 18, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Masahiro UtohHiroshi Yamazaki

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Citations

Mar 25, 2015·Biochemical Pharmacology·Masahiro UtohHiroshi Yamazaki
Apr 22, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shotaro UeharaHiroshi Yamazaki
Jul 16, 2016·Biopharmaceutics & Drug Disposition·Kazuhide IwasakiHiroshi Yamazaki
Jul 29, 2017·Journal of Veterinary Pharmacology and Therapeutics·Y UnoH Yamazaki
Mar 25, 2018·Journal of Medical Primatology·Yasuhiro UnoTeruko Imai
Sep 15, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yasuhiro UnoHiroshi Yamazaki
Aug 9, 2017·Immunogenetics·Zhanna ShubinBhawna Poonia
Oct 26, 2018·Chemical Research in Toxicology·Yasuhiro UnoHiroshi Yamazaki

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