The CYP3A4*18 genotype in the cytochrome P450 3A4 gene, a rapid metabolizer of sex steroids, is associated with low bone mineral density

Clinical Pharmacology and Therapeutics

Volumn 85, Issue 3, 2009, Pages 312-318

  Kang, Y S ^a   Park, S Y ^a   Yim, C H ^a   Kwak, H S ^a   Gajendrarao, P ^b   Krishnamoorthy, N ^b   Yun, S C ^c   Lee, K W ^b   Han, K O ^a  

^a Kwandong University College of Medicine   (South Korea)

^b Gyeongsang National University   (South Korea)

^c University of Ulsan College of Medicine   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 3A4; ESTROGEN; ESTROGEN DERIVATIVE; ESTRONE; MIDAZOLAM; OXYGENASE; SEX HORMONE; TESTOSTERONE; TESTOSTERONE HYDROXYLASE; UNCLASSIFIED DRUG; CYP3A4 PROTEIN, HUMAN; CYTOCHROME P450 3A;

ADULT; AGED; ARTICLE; BONE DENSITY; BONE MASS; CLINICAL FEATURE; CONTROLLED STUDY; ENZYME ACTIVITY; FEMALE; GENE FREQUENCY; GENE MUTATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOTYPE; HEREDITY; HUMAN; HUMAN EXPERIMENT; IN VITRO STUDY; MOLECULAR MODEL; NORMAL HUMAN; OSTEOPOROSIS; PHARMACOGENETICS; PRIORITY JOURNAL; STEROID METABOLISM; WILD TYPE; COMPARATIVE STUDY; ENZYMOLOGY; GENETICS; METABOLISM; MIDDLE AGED; MUTATION; PHYSIOLOGY; PROTEIN CONFORMATION;

ADULT; AGED; BONE DENSITY; CYTOCHROME P-450 CYP3A; FEMALE; GENETIC VARIATION; GENOTYPE; GONADAL STEROID HORMONES; HUMANS; MIDDLE AGED; MUTATION; OSTEOPOROSIS; POLYMORPHISM, GENETIC; PROTEIN CONFORMATION;

EID: 60349106806     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1038/clpt.2008.215     Document Type: Article

References (30)

1. Ralston, S.H. & de Crombrugghe, B. Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev. 20, 2492-2506 (2006).
2. Daly, A.K., Cholerton, S., Gregory, W. & Idle, J.R. Metabolic polymorphisms. Pharmacol. Ther. 57, 129-160 (1993).
3. Westlind, A., Löfberg, L., Tindberg, N., Andersson, T.B. & Sundberg, M. Interindividual differences in hepatic expression of CYP3A4: relationship to genetic polymorphism in the 5′-upstream regulatory region. Biochem. Biophys. Res. Commun. 259, 201-205 (1999).
4. Rogers, J.F., Rocci, M.L. Jr., Haughey, D.B. & Bertino, J.S. Jr. An evaluation of the suitability of intravenous midazolam as an in vivo marker for hepatic cytochrome P4503A activity. Clin. Pharmacol. Ther. 73, 153-158 (2003).
5. Wilkinson, G.R. Drug metabolism and variability among patients in drug response. N. Engl. J. Med. 352, 2211-2221 (2005).
6. Human Cytochrome P450 (CYP) Allele Nomenclature Committee 〈http://www.imm.ki.se/CYPalleles/〉 (2006). Accessed 27 June 2006.
7. Burk, O. & Wojnowski, L. Cytochrome P450 3A and their regulation. Naunyn Schmiedebergs Arch. Pharmacol. 369, 105-124 (2004).
8. Kuehl, P. et al. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat. Genet. 27, 383-391 (2001).
9. Floyd, M.D. et al. Genotype-phenotype associations for common CYP3A4 and CYP3A5 variants in the basal and induced metabolism of midazolam in European- and African-American men and women. Pharmacogenetics 13, 595-606 (2003).
10. Fukushima-Uesaka, H. et al. Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population. Hum. Mutat. 23, 100 (2004).
11. Watkins, P.B. Noninvasive tests of CYP3A enzymes. Pharmacogenetics 4, 171-184 (1994).
12. Streetman, D.S., Bertino, J.S. Jr. & Nafziger, A.N. Phenotyping of drug-metabolizing enzymes in adults: a review of in-vivo cytochrome P450 phenotyping probes. Pharmacogenetics 10, 187-216 (2000).
13. Khan, K.K., He, Y.Q., Domanski, T.L. & Halpert, J.R. Midazolam oxidation by cytochrome P450 3A4 and active-site mutants: an evaluation of multiple binding sites and of the metabolic pathway that leads to enzyme inactivation. Mol. Pharmacol. 61, 495-506 (2002).
14. Dai, D. et al. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J. Pharmacol. Exp. Ther. 299, 825-831 (2001).
15. Lamba, J.K. et al. Common allelic variants of cytochrome P4503A4 and their prevalence in different populations. Pharmacogenetics 12, 121-132 (2002).
16. Hsieh, K.P. et al. Novel mutations of CYP3A4 in Chinese. Drug Metab. Dispos. 29, 268-273 (2001).
17. Park, S.Y., Kang, Y.S., Jeong, M.S., Yoon, H.K. & Han, K.O. Frequencies of CYP3A5 genotypes and haplotypes in a Korean population. J. Clin. Pharm. Ther. 33, 61-65 (2008).
18. Handschin, C. & Meyer, U.A. Induction of drug metabolism: the role of nuclear receptors. Pharmacol. Rev. 55, 649-673 (2003).
19. Leelawattana, R. et al. The oxidative metabolism of estradiol conditions postmenopausal bone density and bone loss. J. Bone Miner. Res. 15, 2513-2520 (2000).
20. Nguyen, T.V., Jones, G., Sambrook, P.N., White, C.P., Kelly, P.J. & Eisman, J.A. Effects of estrogen exposure and reproductive factors on bone mineral density and osteoporotic fractures. J. Clin. Endocrinol. Metab. 80, 2709-2714 (1995).
21. Lee, A.J., Kosh, J.W., Conney, A.H. & Zhu, B.T. Characterization of the NADPH-dependent metabolism of 17beta-estradiol to multiple metabolites by human liver microsomes and selectively expressed human cytochrome P450 3A4 and 3A5. J. Pharmacol. Exp. Ther. 298, 420-432 (2001).
22. Lee, A.J., Mills, L.H., Kosh, J.W., Conney, A.H. & Zhu, B.T. NADPH-dependent metabolism of estrone by human liver microsomes. J. Pharmacol. Exp. Ther. 300, 838-849 (2002).
23. Lee, A.J., Cai, M.X., Thomas, P.E., Conney, A.H. & Zhu, B.T. Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology 144, 3382-3398 (2003).
24. Tsuchiya, Y., Nakajima, M. & Yokoi, T. Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Lett. 227, 115-124 (2005).
25. Kim, S.W., Lim, C.H., Han, K.O., Jung, H.Y., Min, H.K. & Han, I.K. Standardization of dual energy X-ray absorptionmetry (DXA) in spinal BMD of Korean women and phantom. 10th International Congress of Endocrinology, San Francisco, CA 1996. 372.
26. Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254 (1976).
27. Yano, J.K., Wester, M.R., Schoch, G.A., Griffin, K.J., Stout, C.D. & Johnson, E.F. The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution. J. Biol. Chem. 279, 38091-38094 (2004).
28. Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A.E. & Berendsen, H.J. GROMACS: fast, flexible, and free. Comput. Chem. 26, 1701-1718 (2005).
29. Jones, G., Willett, P., Glen, R.C., Leach, A.R. & Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 267, 727-748 (1997).
30. Bento, J.L. et al. Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes. BMC Med. Genet. 6, 42 (2005).