Cytochrome genetic polymorphisms

Luo, H. R., Poland, R., Lin, K. M. Wan, Y. Y. (2006). Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans a cross ethnic comparative study. Clin. Pharmacol. Ther., 80, 33-40. 

It has now been established that genetic polymorphisms in drug metabolizing enzymes such as the cytochrome P450s (CYP) and the phase II enzyme, thiopu-rine methyltransferase, are responsible for inter-individual variability in response and adverse reactions [12, 13]. However, at the present time, the impact of poly-... 

Ingelman-Sundberg, M. (2005) Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6) clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics Journal, 5 (1), 6-13. 

L. W. Wormhoudt, J. N. Commandeur, N. P. Vermeulen, Genetic Polymorphisms of Human V-Acetyltransferase, Cytochrome P450, Glutathione 5-Transferase, and Epoxide Hydrolase Enzymes Relevance to Xenobiotic Metabolism and Toxicity , Crit. Rev. Toxicol. 1999, 29, 59 - 124. 

Cytochromes P450 Genetic Polymorphisms Associated with Nicotine Metabolism... 

Wang H, Tan W, Hao B, Miao X, Zhou G, He F, Lin D (2003a) Substantial reduction in risk of lung adenocarcinoma associated with genetic polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic activation of tobacco-specific carcinogen NNK. Cancer Res 63 8057-8061... 

Desta, Z., Zhao, X., Shin, J.G., and Elockhart, D.A. (2002) Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin. Pharmacokinet. 41, 913-958. 

Data generated from metabolic clearance measurements using liver microsomes can lead to an overestimation of the tme in vivo clearance if the free versus bound fraction is not considered. A useful follow-up assay is therefore plasma protein binding measurement. The impact of cytochrome P-450 inhibition on metabolic clearance of the parent (and thus exposure) is more complicated and it remains rather difficult to make quantitative predictions from in vitro data alone. The reason is that there are generally multiple clearance pathways involved and genetic polymorphism needs to be considered as well. 

Eukasawa, T., Suzuki, A. and Otani, K. (2007) Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines. Journal of Clinical Pharmacy and Therapeutics, 32, 333—341. 

These examples demonstrate that both genetic and environmental factors are involved in determining the activity of this and other cytochrome enzymes. Distinct patterns of genetic polymorphisms exist across ethnic groups and these can be tested and investigated alongside possible environmental and dietary factors that may cause differential expression of these genes. 

Grant DM, Blum M, Meyer UA. Polymorphisms of N-acetyltransferase genes. Xenobiotica 1992 22 1073. Human cytochrome P450s assessment, regulation and genetic polymorphisms. Xenobiotica, 28, number 12, 1998. A series of relevant articles. 

Kirchheiner J, Roots I, Goldammer M, Rosenkranz B, Brockmoller J. Effect of genetic polymorphisms in cytochrome P450 (CYP) 2C9 and CYP2C8 on the pharmacokinetics of oral antidiabetic drugs clinical relevance. Clin Pharmacokinet 2005 44(12) 1209-25. 

Ma, J.D., A.N. Nafziger, and J.S. Bertino, Jr. 2004. Genetic polymorphisms of cytochrome P450 enzymes and the effect on interindividual, pharmacokinetic variability in extensive metabolizers. J Clin Pharmacol 44 447. 

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