Allelic Imbalance (AI) identifies novel tissue-specific cis-regulatory variation for human UGT2B15

Human Mutation

Volumn 31, Issue 1, 2010, Pages 99-107

  Sun, Chang ^a   Southard, Catherine ^a   Witonsky, David B ^a   Olopade, Olufunmilayo I ^a   Di Rienzo, Anna ^a  

^a UNIVERSITY OF CHICAGO   (United States)

Author keywords

AI; Allelic imbalance; Cis regulation; Expression; Tissue specific; UGT2B15

Indexed keywords

GLUCURONOSYLTRANSFERASE; TRANSCRIPTION FACTOR NRF2; UGT2B15 PROTEIN; UNCLASSIFIED DRUG;

ALLELE; ALLELIC IMBALANCE; ARTICLE; BREAST; CELL LINE; CELL STRAIN CACO 2; CELL STRAIN HEPG2; CELL STRAIN LNCAP; CELL STRAIN MCF 7; CHROMATIN IMMUNOPRECIPITATION; COMPARATIVE STUDY; CONTROLLED STUDY; EXON; GENE; GENE CONSTRUCT; GENE EXPRESSION REGULATION; GENE IDENTIFICATION; GENE LINKAGE DISEQUILIBRIUM; HAPLOTYPE; HUMAN; HUMAN CELL; HUMAN TISSUE; LIVER; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN BINDING; REGULATORY MECHANISM; REPORTER GENE; SEQUENCE ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; TISSUE SPECIFICITY;

ALLELIC IMBALANCE; BINDING SITES; BREAST; CHROMATIN IMMUNOPRECIPITATION; ENHANCER ELEMENTS, GENETIC; FEMALE; GENE EXPRESSION REGULATION; GENETIC VARIATION; GLUCURONOSYLTRANSFERASE; HUMANS; LIVER; NF-E2-RELATED FACTOR 2; ORGAN SPECIFICITY;

EID: 74049116628     PISSN: 10597794     EISSN: None     Source Type: Journal    
DOI: 10.1002/humu.21145     Document Type: Article

References (73)

1. Bray NJ, Buckland PR, Owen MJ, O'Donovan MC. 2003a. Cis-acting variation in the expression of a high proportion of genes in human brain. Hum Genet 113: 149-153.
2. Bray NJ, Buckland PR, Williams NM, Williams HJ, Norton N, Owen MJ, O'Donovan MC. 2003b. A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain. Am J Hum Genet 73:152-161.
3. Bray NJ, O'Donovan MC. 2006. Investigating cis-acting regulatory variation using assays of relative allelic expression. Psychiatr Genet 16:173-177.
4. Chan K, Han XD, Kan YW. 2001. An important function of Nrf2 in combating oxidative stress: detoxification of acetaminophen. Proc Natl Acad Sci USA 98:4611-4616.
5. Chen F, Ritter JK, Wang MG, McBride OW, Lubet RA, Owens IS. 1993. Characterization of a cloned human dihydrotestosterone/androstanediol UDP-glucuronosyltransferase and its comparison to other steroid isoforms. Biochemistry 32:10648-10657.
6. Chen X, Weaver J, Bove BA, Vanderveer LA, Weil SC, Miron A, Daly MB, Godwin AK. 2008. Allelic imbalance in BRCA1 and BRCA2 gene expression is associated with an increased breast cancer risk. Hum Mol Genet 17:1336-1348.
7. Cheung VG, Conlin LK, Weber TM, Arcaro M, Jen KY, Morley M, Spielman RS. 2003. Natural variation in human gene expression assessed in lymphoblastoid cells. Nat Genet 33:422-425.
8. Cheung VG, Bruzel A, Burdick JT, Morley M, Devlin JL, Spielman RS. 2008. Monozygotic twins reveal germline contribution to allelic expression differences. Am J Hum Genet 82:1357-1360.
9. Court MH, Hao Q, Krishnaswamy S, Bekaii-Saab T, Al-Rohaimi A, von Moltke LL, Greenblatt DJ. 2004. UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver. J Pharmacol Exp Ther 310:656-665.
10. Ding C, Maier E, Roscher AA, Braun A, Cantor CR. 2004. Simultaneous quantitative and allele-specific expression analysis with real competitive PCR. BMC Genet 5:8.
11. Duan S, Huang RS, Zhang W, Bleibel WK, Roe CA, Clark TA, Chen TX, Schweitzer AC, Blume JE, Cox NJ, Dolan ME. 2008. Genetic architecture of transcript-level variation in humans. Am J Hum Genet 82:1101-1113.
12. Duguay Y, Baar C, Skorpen F, Guillemette C. 2004. A novel functional polymorphism in the uridine diphosphate-glucuronosyltransferase 2B7 promoter with significant impact on promoter activity. Clin Pharmacol Ther 75:223-233.
13. Fukuda Y, Koga M, Arai M, Noguchi E, Ohtsuki T, Horiuchi Y, Ishiguro H, Niizato K, Iritani S, Itokawa M, Arinami T. 2006. Monoallelic and unequal allelic expression of the HTR2A gene in human brain and peripheral lymphocytes. Biol Psychiatry 60:1331-1335.
14. Gardner-Stephen DA, Mackenzie PI. 2008. Liver-enriched transcription factors and their role in regulating UDP glucuronosyltransferase gene expression. Curr Drug Metab 9:439-452.
15. Gsur A, Preyer M, Haidinger G, Schatzl G, Madersbacher S, Marberger M, Vutuc C, Micksche M. 2002. A polymorphism in the UDP-Glucuronosyltransferase 2B15 gene (D85Y) is not associated with prostate cancer risk. Cancer Epidemiol Biomarkers Prev 11:497-498.
16. Guillemette C. 2003. Pharmacogenomics of human UDP- glucuronosyltransferase enzymes. Pharmacogenomics J 3:136-158.
17. Hajdinjak T, Zagradisnik B. 2004. Prostate cancer and polymorphism D85Y in gene for dihydrotestosterone degrading enzyme UGT2B15: frequency of DD homozygotes increases with Gleason score. Prostate 59:436-439.
18. Harrington WR, Sengupta S, Katzenellenbogen BS. 2006. Estrogen regulation of the glucuronidation enzyme UGT2B15 in estrogen receptor-positive breast cancer cells. Endocrinology 147:3843-3850.
19. He CH, Gong P, Hu B, Stewart D, Choi ME, Choi AM, Alam J. 2001. Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. J Biol Chem 276: 20858-20865.
20. He H, Olesnanik K, Nagy R, Liyanarachchi S, Prasad ML, Stratakis CA, Kloos RT, de la Chapelle A. 2005. Allelic variation in gene expression in thyroid tissue. Thyroid 15:660-667.
21. Heighway J, Bowers NL, Smith S, Betticher DC, Koref MF. 2005. The use of allelic expression differences to ascertain functional polymorphisms acting in cis: analysis of MMP1 transcripts in normal lung tissue. Ann Hum Genet 69: 127-133.
22. Hirota T, Ieiri I, Takane H, Maegawa S, Hosokawa M, Kobayashi K, Chiba K, Nanba E, Oshimura M, Sato T, Higuchi S, Otsubo K. 2004. Allelic expression imbalance of the human CYP3A4 gene and individual phenotypic status. Hum Mol Genet 13:2959-2969.
23. Iida A, Saito S, Sekine A, Mishima C, Kitamura Y, Kondo K, Harigae S, Osawa S, 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.
24. Jakobsson J, Lorentzon M, Ohlsson C, Lundmark J, Roh HK, Rane A, Ekstrom L. 2008. Genetic aspects of epitestosterone formation and androgen disposition: influence of polymorphisms in CYP17 and UGT2B enzymes. Pharmacogenet Genomics 18:477-485.
25. Johnson AD, Zhang Y, Papp AC, Pinsonneault JK, Lim JE, Saffen D, Dai Z, Wang D, Sadee W. 2008. Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues. Pharmacogenet Genomics 18:781-791.
26. Jordheim LP, Nguyen-Dumont T, Thomas X, Dumontet C, Tavtigian SV. 2008. Differential allelic expression in leukoblast from patients with acute myeloid leukemia suggests genetic regulation of CDA, DCK, NT5C2, NT5C3, and TP53. Drug Metab Dispos 36:2419-2423.
27. King CD, Rios GR, Green MD, Tephly TR. 2000. UDP- glucuronosyltransferases. Curr Drug Metab 1:143-161.
28. Kristensen VN, Edvardsen H, Tsalenko A, Nordgard SH, Sorlie T, Sharan R, Vailaya A, Ben-Dor A, Lonning PE, Lien S, Omholt S, Syvänen AC, Yakhini Z, Børresen-Dale AL. 2006. Genetic variation in putative regulatory loci controlling gene expression in breast cancer. Proc Natl Acad Sci USA 103:7735-7740.
29. Kwak MK, Itoh K, Yamamoto M, Sutter TR, Kensler TW. 2001. Role of transcription factor Nrf2 in the induction of hepatic phase 2 and antioxidative enzymes in vivo by the cancer chemoprotective agent, 3H-1, 2-dimethiole-3- thione. Mol Med 7:135-145.
30. Lampe JW, Bigler J, Bush AC, 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.
31. Levesque E, Beaulieu M, Green MD, Tephly TR, Belanger A, Hum DW. 1997. Isolation and characterization of UGT2B15(Y85): a UDP-glucuronosyltransferase encoded by a polymorphic gene. Pharmacogenetics 7:317-325.
32. Liu W, Innocenti F, Wu MH, Desai AA, Dolan ME, Cook Jr EH, Ratain MJ. 2005. A functional common polymorphism in a Sp1 recognition site of the epidermal growth factor receptor gene promoter. Cancer Res 65:46-53.
33. Lo HS,Wang Z, Hu Y, Yang HH, Gere S, Buetow KH, Lee MP. 2003. Allelic variation in gene expression is common in the human genome. Genome Res 13:1855-1862.
34. Loeuillet C, Weale M, Deutsch S, Rotger M, Soranzo N, Wyniger J, Lettre G, Dupre Y, Thuillard D, Beckmann JS, Antonarakis SE, Goldstein DB, Telenti A. 2007. Promoter polymorphisms and allelic imbalance in ABCB1 expression. Pharmacogenet Genomics 17:951-959.
35. McCarroll SA, Hadnott TN, Perry GH, Sabeti PC, Zody MC, Barrett JC, Dallaire S, Gabriel SB, Lee C, Daly MJ, Altshuler DM; International HapMap Consortium. 2006. Common deletion polymorphisms in the human genome. Nat Genet 38:86-92.
36. Mackenzie PI, Bock KW, Burchell B, Guillemette C, Ikushiro S, Iyanagi T, Miners JO, Owens IS, Nebert DW. 2005. Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenet Genomics 15:677-685.
37. MacLeod SL, Nowell S, Plaxco J, Lang NP. 2000. An allele-specific polymerase chain reaction method for the determination of the D85Y polymorphism in the human UDP-glucuronosyltransferase 2B15 gene in a case-control study of prostate cancer. Ann Surg Oncol 7:777-782.
38. Mahr S, Burmester GR, Hilke D, Gobel U, Grutzkau A, Haupl T, Hauschild M, Koczan D, Krenn V, Neidel J, Perka C, Radbruch A, Thiesen HJ, Müller B. 2006. Cis- and trans-acting gene regulation is associated with osteoarthritis. Am J Hum Genet 78:793-803.
39. Milani L, Gupta M, Andersen M, Dhar S, Fryknas M, Isaksson A, Larsson R, Syvanen AC. 2007. Allelic imbalance in gene expression as a guide to cis-acting regulatory single nucleotide polymorphisms in cancer cells.Nucleic Acids Res 35:e34.
40. Murakami Y, Isogai K, Tomita H, Sakurai-Yageta M, Maruyama T, Hidaka A, Nose K, Sugano K, Kaneko A. 2004. Detection of allelic imbalance in the gene expression of hMSH2 or RB1 in lymphocytes from pedigrees of hereditary, nonpolyposis, colorectal cancer and retinoblastoma by an RNA difference plot. J Hum Genet 49:635-641.
41. Nakamura A, Nakajima M, Higashi E, Yamanaka H, Yokoi T. 2008a. Genetic polymorphisms in the 5′-flanking region of human UDP- glucuronosyltransferase 2B7 affect the Nrf2-dependent transcriptional regulation. Pharmacogenet Genomics 18:709-720.
42. Nakamura A, Nakajima M, Yamanaka H, Fujiwara R, Yokoi T. 2008b. Expression of UGT1A and UGT2B mRNA in human normal tissues and various cell lines. Drug Metab Dispos 36:1461-1464.
43. Nguyen T, Sherratt PJ, Nioi P, Yang CS, Pickett CB. 2005. Nrf2 controls constitutive and inducible expression of ARE-driven genes through a dynamic pathway involving nucleocytoplasmic shuttling by Keap1. J Biol Chem 280:32485-32492.
44. Ohno S, Nakajin S. 2009. Determination of mRNA expression of human UDP glucuronosyltransferases and application for localization in various human tissues by real-time reverse transcriptase-polymerase chain reaction. Drug Metab Dispos 37:32-40.
45. Pant PV, Tao H, Beilharz EJ, Ballinger DG, Cox DR, Frazer KA. 2006. Analysis of allelic differential expression in human white blood cells. Genome Res 16: 331-339.
46. Park J, Chen L, Shade K, Lazarus P, Seigne J, Patterson S, Helal M, Pow-Sang J. 2004. Asp85tyr polymorphism in the udp-glucuronosyltransferase (UGT) 2B15 gene and the risk of prostate cancer. J Urol 171:2484-2488.
47. Pastinen T, Hudson TJ. 2004. Cis-acting regulatory variation in the human genome. Science 306:647-650.
48. Rockman MV, Kruglyak L. 2006. Genetics of global gene expression. Nat Rev Genet 7:862-872.
49. Schadt EE, Molony C, Chudin E, Hao K, Yang X, Lum PY, Kasarskis A, Zhang B, Wang S, Suver C, Zhu J, Millstein J, Sieberts S, Lamb J, GuhaThakurta D, Derry J, Storey JD, Avila-Campillo I, Kruger MJ, Johnson JM, Rohl CA, van Nas A, Mehrabian M, Drake TA, Lusis AJ, Smith RC, Guengerich FP, Strom SC, Schuetz E, Rushmore TH, Ulrich R. 2008. Mapping the genetic architecture of gene expression in human liver. PLoS Biol 6:e107.
50. Serre D, Gurd S, Ge B, Sladek R, Sinnett D, Harmsen E, Bibikova M, Chudin E, Barker DL, Dickinson T, Fan JB, Hudson TJ. 2008. Differential allelic expression in the human genome: a robust approach to identify genetic and epigenetic cis-acting mechanisms regulating gene expression. PLoS Genet 4:e1000006.
51. Sparks R, Ulrich CM, Bigler J, Tworoger SS, Yasui Y, Rajan KB, Porter P, Stanczyk FZ, Ballard-Barbash R, Yuan X, Lin MG, McVarish L, Aiello EJ, McTiernan A. 2004. UDP-glucuronosyltransferase and sulfotransferase polymorphisms, sex hormone concentrations, and tumor receptor status in breast cancer patients. Breast Cancer Res 6:R488-R498.
52. Stamatoyannopoulos JA. 2004. The genomics of gene expression. Genomics 84: 449-457.
53. Stephens M, Donnelly P. 2003. A comparison of Bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet 73:1162-1169.
54. Stephens M, Sloan JS, Robertson PD, Scheet P, Nickerson DA. 2006. Automating sequence-based detection and genotyping of SNPs from diploid samples. Nat Genet 38:375-381.
55. Stranger BE, Nica AC, Forrest MS, Dimas A, Bird CP, Beazley C, Ingle CE, Dunning M, Flicek P, Koller D, Montgomery S, Tavaré S, Deloukas P, Dermitzakis ET. 2007. Population genomics of human gene expression. Nat Genet 39:1217-1224.
56. Swanson C, Mellstrom D, Lorentzon M, Vandenput L, Jakobsson J, Rane A, Karlsson M, Ljunggren O, Smith U, Eriksson AL, Bélanger A, Labrie F, Ohlsson C. 2007. The uridine diphosphate glucuronosyltransferase 2B15 D85Y and 2B17 deletion polymorphisms predict the glucuronidation pattern of androgens and fat mass in men. J Clin Endocrinol Metab 92:4878-4882.
57. Tao H, Cox DR, Frazer KA. 2006. Allele-specific KRT1 expression is a complex trait. PLoS Genet 2:e93.
58. Tchernof A, Levesque E, Beaulieu M, Couture P, Despres JP, Hum DW, Belanger A. 1999. Expression of the androgen metabolizing enzyme UGT2B15 in adipose tissue and relative expression measurement using a competitive RT-PCR method. Clin Endocrinol (Oxf) 50:637-642.
59. Tukey RH, Strassburg CP. 2000. Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 40:581-616.
60. Turgeon D, Carrier JS, Levesque E, Beatty BG, Belanger A, Hum DW. 2000. Isolation and characterization of the human UGT2B15 gene, localized within a cluster of UGT2B genes and pseudogenes on chromosome 4. J Mol Biol 295:489-504.
61. Turgeon D, Carrier JS, Levesque E, Hum DW, Belanger A. 2001. Relative enzymatic activity, protein stability, and tissue distribution of human steroid-metabolizing UGT2B subfamily members. Endocrinology 142:778-787.
62. Tuupanen S, Niittymaki I, Nousiainen K, Vanharanta S, Mecklin JP, Nuorva K, Jarvinen H, Hautaniemi S, Karhu A, Aaltonen LA. 2008. Allelic imbalance at rs6983267 suggests selection of the risk allele in somatic colorectal tumor evolution. Cancer Res 68:14-17.
63. Tycko B, Morison IM. 2002. Physiological functions of imprinted genes. J Cell Physiol 192:245-258.
64. Udler M, Maia AT, Cebrian A, Brown C, Greenberg D, Shah M, Caldas C, Dunning A, Easton D, Ponder B, Pharoah P. 2007. Common germline genetic variation in antioxidant defense genes and survival after diagnosis of breast cancer. J Clin Oncol 25:3015-3023.
65. Valle L, Serena-Acedo T, Liyanarachchi S, Hampel H, Comeras I, Li Z, Zeng Q, Zhang HT, Pennison MJ, Sadim M, Pasche B, Tanner SM, de la Chapelle A. 2008. Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer. Science 321:1361-1365.
66. Wang H, Elbein S. 2007. Detection of allelic imbalance in gene expression using pyrosequencing. Methods Mol Biol 373:157-175.
67. Ware MD, DeSilva D, Sinilnikova OM, Stoppa-Lyonnet D, Tavtigian SV, Mazoyer S. 2006. Does nonsense-mediated mRNA decay explain the ovarian cancer cluster region of the BRCA2 gene? Oncogene 25:323-328.
68. Wegman P, Elingarami S, Carstensen J, Stal O, Nordenskjold B, Wingren S. 2007. Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer. Breast Cancer Res 9:R7.
69. Wilkins JM, Southam L, Price AJ, Mustafa Z, Carr A, Loughlin J. 2007. Extreme context specificity in differential allelic expression. Hum Mol Genet 16:537-546.
70. Xue Y, Sun D, Daly A, Yang F, Zhou X, Zhao M, Huang N, Zerjal T, Lee C, Carter NP, Hurles ME, Tyler-Smith C. 2008. Adaptive evolution of UGT2B17 copy-number variation. Am J Hum Genet 83:337-346.
71. Yan H, Yuan W, Velculescu VE, Vogelstein B, Kinzler KW. 2002. Allelic variation in human gene expression. Science 297:1143.
72. Yan H, Zhou W. 2004. Allelic variations in gene expression. Curr Opin Oncol 16:39-43.
73. Zhang Y, Wang D, Johnson AD, Papp AC, Sadee W. 2005. Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. J Biol Chem 280:32618-32624.