UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver

Journal of Pharmacology and Experimental Therapeutics

Volumn 310, Issue 2, 2004, Pages 656-665

  Court, Michael H ^a,c   Hao, Qin ^a   Krishnaswamy, Soundararajan ^a   Bekaii Saab, Tanios ^a,b   Al Rohaimi, Abdul ^a   Von Moltke, Lisa L ^a   Greenblatt, David J ^a  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b OHIO STATE UNIVERSITY   (United States)

^c TUFTS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASPARTIC ACID; GLUCURONOSYLTRANSFERASE; GLUCURONOSYLTRANSFERASE 2B15; OXAZEPAM; TYROSINE; UNCLASSIFIED DRUG;

ADOLESCENT; ADULT; AGED; ARTICLE; CHILD; CONTROLLED STUDY; DNA ISOLATION; DNA POLYMORPHISM; DRUG GLUCURONIDATION; DRUG METABOLISM; FEMALE; GENDER; GENE FREQUENCY; GENE SEQUENCE; GENE STRUCTURE; GENOTYPE; HUMAN; HUMAN TISSUE; LIVER METABOLISM; LIVER MICROSOME; MALE; NUCLEOTIDE SEQUENCE; PHARMACOGENETICS; PHENOTYPE; PRIORITY JOURNAL; SEX DIFFERENCE;

ADOLESCENT; ADULT; AGED; ANALYSIS OF VARIANCE; CHILD; CHILD, PRESCHOOL; FEMALE; GENOTYPE; GLUCURONIDES; GLUCURONOSYLTRANSFERASE; HUMANS; LIVER; MALE; MIDDLE AGED; OXAZEPAM; POLYMORPHISM, SINGLE NUCLEOTIDE; SEX CHARACTERISTICS; STATISTICS, NONPARAMETRIC;

EID: 3343026223     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: 10.1124/jpet.104.067660     Document Type: Article

References (28)

1. Barbier O, Turgeon D, Girard C, Green MD, Tephly TR, Hum DW, and Belanger A (2000) 3′-Azido-3′-deoxythimidine (AZT) is glucuronidated by human UDP-glucuronosyltransferase 2B7 (UGT2B7). Drug Metab Dispos 28:497-502.
2. Bhasker CR, McKinnon W, Stone A, Lo AC, Kubota T, Ishizaki T, and Miners JO (2000) Genetic polymorphism of UDP-glucuronosyltransferase 2B7 (UGT2B7) at amino acid 268: ethnic diversity of alleles and potential clinical significance. Pharmacogenetics 10:679-685.
3. Chen F, Ritter JK, Wang MG, McBride OW, Lubet RA, and Owens IS (1993) Characterization of a cloned human dihydrotestosterone/androstanediol UDP-glucuronosyltransferase and its comparison to other steroid isoforms. Biochemistry 32:10648-10657.
4. Ciotti M, Marrone A, Potter C, and Owens IS (1997) Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications. Pharmacogenetics 7:485-495.
5. Coffman BL, King CD, Rios GR, and Tephly TR (1998) The glucuronidation of opioids, other xenobiotics and androgens by human UGT2B7Y(268) and UGT2B7H(268). Drug Metab Dispos 26:73-77.
6. Court MH, Duan SX, Guillemette C, Journault K, Krishnaswamy S, Von Moltke LL, and Greenblatt DJ (2002) Stereoselective conjugation of oxazepam by human UDP-glucuronosyltransferases (UGTs): S-oxazepam is glucuronidated by UGT2B15, while R-oxazepam is glucuronidated by UGT2B7 and UGT1A9. Drug Metab Dispos 30:1257-1265.
7. Court MH, Krishnaswamy S, Hao Q, Duan SX, Patten CJ, Von Moltke LL, and Greenblatt DJ (2003) Evaluation of 3′-azido-3′-deoxythymidine, morphine and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B7*2 polymorphism. Drug Metab Dispos 31:1125-1133.
8. Court MH, Von Moltke LL, Shader RI, and Greenblatt DJ (1997) Biotransformation of chlorzoxazone by hepatic microsomes from humans and ten other mammalian species. Biopharm Drug Dispos 18:213-226.
9. Green M, Oturo E, and Tephly T (1994) Stable expression of a human liver UDP-glucuronosyltransferase (UGT2B15) with activity toward steroid and xenobiotic substrates. Drug Metab Dispos 22:799-805.
10. Greenblatt DJ (1981) Clinical pharmacokinetics of oxazepam and lorazepam. Clin Pharmacokinet 6:89-105.
11. Greenblatt DJ, Abernethy DR, Koepke HH, and Shader RI (1984) Interaction of cimetidine with oxazepam, lorazepam and flurazepam. J Clin Pharmacol 24:187-193.
12. Greenblatt DJ, Divoll M, Harmatz JS, and Shader RI (1980) Oxazepam kinetics: effects of age and sex. J Pharmacol Exp Ther 215:86-91.
13. Guillemette C, Ritter JK, Auyeung DJ, Kessler FK, and Housman DE (2000) Structural heterogeneity at the UDP-glucuronosyltransferase 1 locus: functional consequences of three novel missense mutations in the human UGT1A7 gene. Pharmacogenetics 10:629-644.
14. Holthe M, Klepstad P, Zahlsen K, Borchgrevink PC, Hagen L, Dale O, Kaasa S, Krokan HE, and Skorpen F (2002) Morphine glucaronide-to-morphine plasma ratios are unaffected by the UGT2B7 H268Y and UGT1A1*28 polymorphisms in cancer patients on chronic morphine therapy. Eur J Clin Pharmacol 58:353-356.
15. Iida A, Saito S, Sekine A, Mishima C, Kitamura Y, Kondo K, Harigae S, Osawa S, and Nakamura Y (2002) Catalog of 86 single-nucleotide polymorphisms (SNPs) in three uridine diphosphate glycosyltransferase genes: UGT2A1, UGT2B15 and UGT8. J Hum Genet 47:505-510.
16. Jin C, Miners J, Lillywhite K, and Mackenzie P (1993) Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphateglucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J Pharmacol Exp Ther 264:475-479.
17. Kuuranne T, Kurkela M, Thevis M, Schanzer W, Finel M, and Kostiainen R (2003) Glucuronidation of anabolic androgenic steroids by recombinant human UDP-glucuronosyltransferases. Drug Metab Dispos 31:1117-1124.
18. Lampe JW, Bigler J, Bush AC, and Potter JD (2000) Prevalence of polymorphisms in the human UDP-glucuronosyltransferase 2B family: UGT2B4(D458E), UGT2B7(H268Y) and UGT2B15(D85Y). Cancer Epidemiol Biomarkers Prev 9:329-333.
19. Levesque E, Beaulieu M, Green MD, Tephly TR, Belanger A, and Hum DW (1997) Isolation and characterization of UGT2B15(Y85): a UDP- glueuronosyltransferase encoded by a polymorphic gene. Pharmacogenetics 7:317-325.
20. Levesque E, Beaulieu M, Hum DW, and Belanger A (1999) Characterization and substrate specificity of UGT2B4 (E458): a UDP-glucuronosyltransferase encoded by a polymorphic gene. Pharmacogenetics 9:207-216.
21. Nishiyama T, Ogura K, Nakano H, Ohnuma T, Kaku T, Hiratsuka A, Muro K, and Watabe T (2002) Reverse geometrical selectivity in glucuronidation and sulfation of cis-and trans-4-hydroxytamoxifens by human liver UDP-glucuronosyltransferases and sulfotransferases. Biochem Pharmacol 63:1817-1830.
22. Patel M, Tang BK, Grant DM, and Kalow W (1995a) Interindividual variability in the glucuronidation of (S) oxazepam contrasted with that of (R) oxazepam. Pharmacogenetics 5:287-297.
23. Patel M, Tang BK, and Kalow W (1995b) (S)oxazepam glucuronidation is inhibited by ketoprofen and other substrates of UGT2B7. Pharmacogenetics 5:43-49.
24. Schneider S, Roessli D, and Excofier L (2001) Arlequin, in Genetics and Biometry Laboratory. University of Geneva, Geneva, Switzerland.
25. Sonne J (1993) Factors and conditions affecting the glucuronidation of oxazepam. Pharmacol Toxicol 73 (Suppl 1):1-23.
26. Stephens M, Smith NJ, and Donnelly P (2001) A new statistical method for haplo-type reconstruction from population data. Am J Hum Genet 68:978-989.
27. Yang SK and Lu XL (1989) Racemization kinetics of enantiomeric oxazepams and stereoselective hydrolysis of enantiomeric oxazepam 3-acetates in rat liver microsomes and brain homogenate. J Pharm Sci 78:789-795.
28. Zhang JY, Zhan J, Cook CS, Ings RM, and Breau AP (2003) Involvement of human UGT2B7 and 2B15 in rofecoxib metabolism. Drug Metab Dispos 31:652-658.