This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lampe, J. W. Articles by Potter, J. D. Search for Related Content PubMed PubMed Citation Articles by Lampe, J. W. Articles by Potter, J. D.

Prevalence of Polymorphisms in the Human UDP-Glucuronosyltransferase 2B Family: UGT2B4(D⁴⁵⁸E), UGT2B7(H²⁶⁸Y), and UGT2B15(D⁸⁵Y)¹

Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024

UDP-glucuronosyltransferases (UGTs) of the UGT2B family conjugate steroid hormones as well as bile acids and xenobiotics. UGT2Bs are expressed in numerous human tissues, such as skin, breast, prostate, adipose, and intestine and are hypothesized to modulate steroid metabolism and excretion. Polymorphisms have been identified that may modify substrate specificities or enzyme activities of UGT2B family isozymes. We determined the prevalence of the UGT2B4(D⁴⁵⁸E), UGT2B7(H²⁶⁸Y), and UGT2B15(D⁸⁵Y) polymorphisms in a sample of 233 individuals. The allele frequencies were significantly different (P < 0.02) between individuals of Caucasian and Asian descent for all three polymorphisms. In Asians (n = 32), the frequencies of the UGT2B4(D⁴⁵⁸), UGT2B7(H²⁶⁸), and UGT2B15(D⁸⁵) alleles were 1.00, 0.73, and 0.64, respectively, whereas, in Caucasians (n = 202), the frequencies of UGT2B4(D⁴⁵⁸), UGT2B7(H²⁶⁸), and UGT2B15(D⁸⁵) were 0.75, 0.46, and 0.45, respectively. The distribution of the UGT2B4(D⁴⁵⁸E), UGT2B7(H²⁶⁸Y), and UGT2B15(D⁸⁵Y) genotypes also differed by ethnic group (P < 0.0001, P = 0.002, and P = 0.02, respectively). All Asians were homozygous for UGT2B4(D⁴⁵⁸) and had a greater than 2-fold higher prevalence of the UGT2B7(H²⁶⁸) and UGT2B15(D⁸⁵) homozygous genotypes compared with Caucasians: 56.2% versus 21.8%, and 46.9% versus 22.3%, respectively. Concomitantly, only 9.4% of Asians were UGT2B7(Y²⁶⁸) homozygous and 18.7% were UGT2B15(Y⁸⁵) homozygous compared with 29.2% and 32.2%, respectively, of Caucasians. The data suggest that there may be large differences in UGT2B polymorphisms between Asians and Caucasians. This warrants evaluation both in larger, multiethnic cohorts and in relation to known ecological differences in risk of sex hormone-dependent cancers.

This article has been cited by other articles:

				C. Swanson, M. Lorentzon, L. Vandenput, F. Labrie, A. Rane, J. Jakobsson, S. Chouinard, A. Belanger, and C. Ohlsson Sex Steroid Levels and Cortical Bone Size in Young Men Are Associated with a Uridine Diphosphate Glucuronosyltransferase 2B7 Polymorphism (H268Y) J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3697 - 3704. [Abstract] [Full Text] [PDF]

				O. Bernard, J. Tojcic, K. Journault, L. Perusse, and C. Guillemette Influence of Nonsynonymous Polymorphisms of UGT1A8 and UGT2B7 Metabolizing Enzymes on the Formation of Phenolic and Acyl Glucuronides of Mycophenolic Acid Drug Metab. Dispos., September 1, 2006; 34(9): 1539 - 1545. [Abstract] [Full Text] [PDF]

				J. R. Ross, J. Riley, C. Quigley, and K. I. Welsh Clinical Pharmacology and Pharmacotherapy of Opioid Switching in Cancer Patients Oncologist, July 1, 2006; 11(7): 765 - 773. [Abstract] [Full Text] [PDF]

				G. E. Kuehl, J. Bigler, J. D. Potter, and J. W. Lampe GLUCURONIDATION OF THE ASPIRIN METABOLITE SALICYLIC ACID BY EXPRESSED UDP-GLUCURONOSYLTRANSFERASES AND HUMAN LIVER MICROSOMES Drug Metab. Dispos., February 1, 2006; 34(2): 199 - 202. [Abstract] [Full Text] [PDF]

				J. Jakobsson, L. Ekstrom, N. Inotsume, M. Garle, M. Lorentzon, C. Ohlsson, H.-K. Roh, K. Carlstrom, and A. Rane Large Differences in Testosterone Excretion in Korean and Swedish Men Are Strongly Associated with a UDP-Glucuronosyl Transferase 2B17 Polymorphism J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 687 - 693. [Abstract] [Full Text] [PDF]

				G. E. Kuehl, J. W. Lampe, J. D. Potter, and J. Bigler GLUCURONIDATION OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS: IDENTIFYING THE ENZYMES RESPONSIBLE IN HUMAN LIVER MICROSOMES Drug Metab. Dispos., July 1, 2005; 33(7): 1027 - 1035. [Abstract] [Full Text] [PDF]

				M. Saeki, Y. Saito, H. Jinno, T. Tanaka-Kagawa, A. Ohno, S. Ozawa, K. Ueno, S. Kamakura, N. Kamatani, K. Komamura, et al. SINGLE NUCLEOTIDE POLYMORPHISMS AND HAPLOTYPE FREQUENCIES OF UGT2B4 AND UGT2B7 IN A JAPANESE POPULATION Drug Metab. Dispos., September 1, 2004; 32(9): 1048 - 1054. [Abstract] [Full Text] [PDF]

				M. H. Court, Q. Hao, S. Krishnaswamy, T. Bekaii-Saab, A. Al-Rohaimi, L. L. von Moltke, and D. J. Greenblatt UDP-Glucuronosyltransferase (UGT) 2B15 Pharmacogenetics: UGT2B15 D85Y Genotype and Gender Are Major Determinants of Oxazepam Glucuronidation by Human Liver J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 656 - 665. [Abstract] [Full Text] [PDF]

				P. G. Wells, P. I. Mackenzie, J. Roy Chowdhury, C. Guillemette, P. A. Gregory, Y. Ishii, A. J. Hansen, F. K. Kessler, P. M. Kim, N. Roy Chowdhury, et al. GLUCURONIDATION AND THE UDP-GLUCURONOSYLTRANSFERASES IN HEALTH AND DISEASE Drug Metab. Dispos., March 1, 2004; 32(3): 281 - 290. [Abstract] [Full Text] [PDF]

				C. Girard, O. Barbier, G. Veilleux, M. El-Alfy, and A. Belanger Human Uridine Diphosphate-Glucuronosyltransferase UGT2B7 Conjugates Mineralocorticoid and Glucocorticoid Metabolites Endocrinology, June 1, 2003; 144(6): 2659 - 2668. [Abstract] [Full Text] [PDF]

				J. Y. Zhang, J. Zhan, C. S. Cook, R. M. Ings, and A. P. Breau Involvement of Human UGT2B7 and 2B15 in Rofecoxib Metabolism Drug Metab. Dispos., May 1, 2003; 31(5): 652 - 658. [Abstract] [Full Text] [PDF]

				M. H. Court, S. X. Duan, C. Guillemette, K. Journault, S. Krishnaswamy, L. L. von Moltke, and D. J. Greenblatt 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., November 1, 2002; 30(11): 1257 - 1265. [Abstract] [Full Text] [PDF]

				A. Gsur, M. Preyer, G. Haidinger, G. Schatzl, S. Madersbacher, M. Marberger, C. Vutuc, and M. Micksche A Polymorphism in the UDP-Glucuronosyltransferase 2B15 Gene (D85Y) Is Not Associated with Prostate Cancer Risk Cancer Epidemiol. Biomarkers Prev., May 1, 2002; 11(5): 497 - 498. [Full Text] [PDF]

				R. Elsby, J. L. Maggs, J. Ashby, and B. K. Park Comparison of the Modulatory Effects of Human and Rat Liver Microsomal Metabolism on the Estrogenicity of Bisphenol A: Implications for Extrapolation to Humans J. Pharmacol. Exp. Ther., April 1, 2001; 297(1): 103 - 113. [Abstract] [Full Text]