Effects of the CYP Oxidoreductase Ala503Val Polymorphism on CYP3A Activity In Vivo: A Randomized, Open-Label, Crossover Study in Healthy Chinese Men

Clinical Therapeutics

Volumn 33, Issue 12, 2011, Pages 2060-2070

  Yang, Guoping ^a   Fu, Zhimin ^a   Chen, Xiaoping ^a   Yuan, Hong ^a   Yang, Heng ^a   Huang, Yuanyuan ^a   Ouyang, Dongsheng ^a   Tan, Zhirong ^a   Tan, Hongyi ^a   Huang, Zhijun ^a   Zhou, Honghao ^a  

^a CENTRAL SOUTH UNIVERSITY   (China)

Author keywords

Chinese; CYP3A; Midazolam; P450 oxidoreductase; Polymorphism

Indexed keywords

1 HYDROXYMIDAZOLAM; CYTOCHROME C OXIDASE; CYTOCHROME P450 3A; DRUG METABOLITE; MIDAZOLAM; UNCLASSIFIED DRUG;

AREA UNDER THE CURVE; ARTICLE; CHINESE; CROSSOVER PROCEDURE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFECT; DRUG HALF LIFE; ENZYME ACTIVITY; GENETIC POLYMORPHISM; GENOTYPE; HUMAN; HUMAN EXPERIMENT; IN VIVO STUDY; MAXIMUM PLASMA CONCENTRATION; META ANALYSIS; PHENOTYPE; RANDOMIZED CONTROLLED TRIAL; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; ADULT; ANALYSIS OF VARIANCE; ASIAN CONTINENTAL ANCESTRY GROUP; BIOTRANSFORMATION; CHINA; CHROMATOGRAPHY, LIQUID; CROSS-OVER STUDIES; CYTOCHROME P-450 CYP3A; GENE FREQUENCY; HETEROZYGOTE; HOMOZYGOTE; HUMANS; HYDROXYLATION; INJECTIONS, INTRAVENOUS; INTESTINES; LIVER; MALE; MIDAZOLAM; NADPH-FERRIHEMOPROTEIN REDUCTASE; PHENOTYPE; POLYMORPHISM, GENETIC; SEX FACTORS; TANDEM MASS SPECTROMETRY; YOUNG ADULT;

EID: 83455225481     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2011.11.004     Document Type: Article

References (42)

1. Flockhart D.A., Rae J.M. Cytochrome P450 3A pharmacogenetics: the road that needs traveled. Pharmacogenomics J 2003, 3:3-5.
2. Evans W.E., Relling M.V. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999, 286:487-491.
3. Wojnowski L., Kamdem L.K. Clinical implications of CYP3A polymorphisms. Expert Opin Drug Metab Toxicol 2006, 2:171-182.
4. Lamba J.K., Lin Y.S., Schuetz E.G., Thummel K.E. Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 2002, 54:1271-1294.
5. Ozdemir V., Kalow W., Tang B.K., et al. Evaluation of the genetic component of variability in CYP3A4 activity: a repeated drug administration method. Pharmacogenetics 2000, 10:373-388.
6. Chen X., Wang H., Zhou G., et al. Molecular population genetics of human CYP3A locus: signatures of positive selection and implications for evolutionary environmental medicine. Environ Health Perspect 2009, 117:1541-1548.
7. Koyano S., Kurose K., Saito Y., et al. Functional characterization of four naturally occurring variants of human pregnane X receptor (PXR): one variant causes dramatic loss of both DNA binding activity and the transactivation of the CYP3A4 promoter/enhancer region. Drug Metab Dispos 2004, 32:149-154.
8. Lamba J., Lamba V., Schuetz E. Genetic variants of PXR (NR1I2) and CAR (NR1I3) and their implications in drug metabolism and pharmacogenetics. Curr Drug Metab 2005, 6:369-383.
9. Ikeda S., Kurose K., Jinno H., et al. Functional analysis of four naturally occurring variants of human constitutive androstane receptor. Mol Genet Metab 2005, 86:314-319.
10. Lamba J., Strom S., Venkataramanan R., et al. MDR1 genotype is associated with hepatic cytochrome P450 3A4 basal and induction phenotype. Clin Pharmacol Ther 2006, 79:325-338.
11. Letschert K., Keppler D., Konig J. Mutations in the SLCO1B3 gene affecting the substrate specificity of the hepatocellular uptake transporter OATP1B3 (OATP8). Pharmacogenetics 2004, 14:441-452.
12. Michalski C., Cui Y., Nies A.T., et al. A naturally occurring mutation in the SLC21A6 gene causing impaired membrane localization of the hepatocyte uptake transporter. J Biol Chem 2002, 277:43058-43063.
13. Nozawa T., Nakajima M., Tamai I., et al. Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis. J Pharmacol Exp Ther 2002, 302:804-813.
14. Tirona R.G., Leake B.F., Merino G., Kim R.B. Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. J Biol Chem 2001, 276:35669-35675.
15. Huang N., Agrawal V., Giacomini K.M., Miller W.L. Genetics of P450 oxidoreductase: sequence variation in 842 individuals of four ethnicities and activities of 15 missense mutations. Proc Natl Acad Sci U S A 2008, 105:1733-1738.
16. Scott R.R., Gomes L.G., Huang N., et al. Apparent manifesting heterozygosity in P450 oxidoreductase deficiency and its effect on coexisting 21-hydroxylase deficiency. J Clin Endocrinol Metab 2007, 92:2318-2322.
17. Munro A.W., Noble M.A., Robledo L., et al. Determination of the redox properties of human NADPH-cytochrome P450 reductase. Biochemistry 2001, 40:1956-1963.
18. Hubbard P.A., Shen A.L., Paschke R., et al. NADPH-cytochrome P450 oxidoreductase. Structural basis for hydride and electron transfer. J Biol Chem 2001, 276:29163-29170.
19. Wang M., Roberts D.L., Paschke R., et al. Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes. Proc Natl Acad Sci U S A 1997, 94:8411-8416.
20. Miller W.L. Minireview: regulation of steroidogenesis by electron transfer. Endocrinology 2005, 146:2544-2550.
21. Gu J., Weng Y., Zhang Q.Y., et al. Liver-specific deletion of the NADPH-cytochrome P450 reductase gene: impact on plasma cholesterol homeostasis and the function and regulation of microsomal cytochrome P450 and heme oxygenase. J Biol Chem 2003, 278:25895-25901.
22. Henderson C.J., Otto D.M., Carrie D., et al. Inactivation of the hepatic cytochrome P450 system by conditional deletion of hepatic cytochrome P450 reductase. J Biol Chem 2003, 278:13480-13486.
23. Huang N., Pandey A.V., Agrawal V., et al. Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis. Am J Hum Genet 2005, 76:729-749.
24. Gomes L.G., Huang N., Agrawal V., et al. The common P450 oxidoreductase variant A503V is not a modifier gene for 21-hydroxylase deficiency. J Clin Endocrinol Metab 2008, 93:2913-2916.
25. Gomes A.M., Winter S., Klein K., et al. Pharmacogenomics of human liver cytochrome P450 oxidoreductase: multifactorial analysis and impact on microsomal drug oxidation. Pharmacogenomics 2009, 10:579-599.
26. Agrawal V., Huang N., Miller W.L. Pharmacogenetics of P450 oxidoreductase: effect of sequence variants on activities of CYP1A2 and CYP2C19. Pharmacogenet Genomics 2008, 18:569-576.
27. Oneda B., Crettol S., Jaquenoud Sirot E., et al. The P450 oxidoreductase genotype is associated with CYP3A activity in vivo as measured by the midazolam phenotyping test. Pharmacogenet Genomics 2009, 19:877-883.
28. McConn D.J., Lin Y.S., Mathisen T.L., et al. Reduced duodenal cytochrome P450 3A protein expression and catalytic activity in patients with cirrhosis. Clin Pharmacol Ther 2009, 5:387-393.
29. Garsa A.A., McLeod H.L., Marsh S. CYP3A4 and CYP3A5 genotyping by Pyrosequencing. BMC Med Genet 2005, 6:19.
30. Eap C.B., Buclin T., Hustert E., et al. Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects. Eur J Clin Pharmacol 2004, 60:231-236.
31. Eap C.B., Fellay J., Buclin T., et al. CYP3A activity measured by the midazolam test is not related to 3435 C >T polymorphism in the multiple drug resistance transporter gene. Pharmacogenetics 2004, 14:255-260.
32. Shiran M.R., Gregory A., Rostami-Hodjegan A., et al. Determination of midazolam and 1'-hydroxymidazolam by liquid chromatography-mass spectrometry in plasma of patients undergoing methadone maintenance treatment. J Chromatogr B Analyt Technol Biomed Life Sci 2003, 783:303-307.
33. Kim K.A., Park P.W., Lee O.J., et al. Effect of CYP3A5*3 genotype on the pharmacokinetics and pharmacodynamics of amlodipine in healthy Korean subjects. Clin Pharmacol Ther 2006, 80:646-656.
34. Kanazawa H., Okada A., Igarashi E., et al. Determination of midazolam and its metabolite as a probe for cytochrome P450 3A4 phenotype by liquid chromatography-mass spectrometry. J Chromatogr A 2004, 1031:213-218.
35. Schirmer M., Rosenberger A., Klein K., et al. Sex-dependent genetic markers of CYP3A4 expression and activity in human liver microsomes. Pharmacogenomics 2007, 8:443-453.
36. Gorski J.C., Hall S.D., Jones D.R., et al. Regioselective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamily. Biochem Pharmacol 1994, 47:1643-1653.
37. Kuehl P., Zhang J., Lin Y., et al. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 2001, 27:383-391.
38. Xiang Q., Zhao X., Zhou Y., et al. Effect of CYP2D6, CYP3A5, and MDR1 genetic polymorphisms on the pharmacokinetics of risperidone and its active moiety. J Clin Pharmacol 2010, 50:659-666.
39. Chen B., Zhang W., Fang J., et al. Influence of the MDR1 haplotype and CYP3A5 genotypes on cyclosporine blood level in Chinese renal transplant recipients. Xenobiotica 2009, 39:931-938.
40. Zhao Y., Zhai D., He H., et al. Effects of CYP3A5, MDR1 and CACNA1C polymorphisms on the oral disposition and response of nimodipine in a Chinese cohort. Eur J Clin Pharmacol 2009, 65:579-584.
41. Agrawal V., Choi J.H., Giacomini K.M., Miller W.L. Substrate-specific modulation of CYP3A4 activity by genetic variants of cytochrome P450 oxidoreductase. Pharmacogenet Genomics 2010, 20:611-618.
42. Canaparo R., Finnstrom N., Serpe L., et al. Expression of CYP3A isoforms and P-glycoprotein in human stomach, jejunum and ileum. Clin Exp Pharmacol Physiol 2007, 34:1138-1144.