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Review Article

Gilbert-Meulengracht’s syndrome and pharmacogenetics: is jaundice just the tip of the iceberg?

Pages 168-181 | Accepted 27 Jul 2009, Published online: 05 Oct 2009

References

  • Adegoke, O. J., Shu, X. O., Gao, Y. T., Cai, Q., Breyer, J., Smith, J., et al. (2004). Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) and risk of breast cancer. Breast Cancer Res Treat 85:239–245.
  • Ando, Y., Chida, M., Nakayama, K., Saka, H., Kamataki, T. (1998a). The UGT1A1*28 allele is relatively rare in a Japanese population. Pharmacogenetics 8:357–360.
  • Ando, Y., Saka, H., Asai, G., Sugiura, S., Shimokata, K., Kamataki, T. (1998b). UGT1A1 genotypes and glucuronidation of SN-38, the active metabolite of irinotecan. Ann Oncol 9:845–847.
  • Aono, S., Adachi, Y., Uyama, E., Yamada, Y., Keino, H., Nanno, T., et al. (1995). Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert’s syndrome [see comments]. Lancet 345:958–959.
  • Aono, S., Yamada, Y., Keino, H., Hanada, N., Nakagawa, T., Sasaoka, Y., et al. (1993). Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-najjar syndrome type II. Biochem Biophys Res Commun 197:1239–1244.
  • Aono, S., Yamada, Y., Keino, H., Sasaoka, Y., Nakagawa, T., Onishi, S., et al. (1994). A new type of defect in the gene for bilirubin uridine 5’-diphosphate-glucuronosyltransferase in a patient with Crigler-najjar syndrome type I. Pediatr Res 35:629–632.
  • Arias, I. M. (1962). Chronic unconjugated hyperbilirubinemia without signs of overt hemolysis in adolescents and adults. J Clin Invest 41:2233–2245.
  • Balram, C., Sabapathy, K., Fei, G., Khoo, K. S., Lee, E. J. (2002). Genetic polymorphisms of UDP-glucuronosyltransferase in Asians: UGT1A1*28 is a common allele in Indians. Pharmacogenetics 12:81–83.
  • Berk, P. D., Blaschke, T. F., Waggoner, J. G. (1972). Defective bromosulfophthalein clearance in patients with constitutional hepatic dysfunction (Gilbert’s syndrome). Gastroenterology 63:472–481.
  • Beutler, E., Gelbart, T., Demina, A. (1998). Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci U S A 95:8170–8174.
  • Bosma, P. J., Chowdhury, J. R., Bakker, C., Gantla, S., de Boer, A., Oostra, B. A., et al. (1995). The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome [see comments]. NEJM 333:1171–1175.
  • Bosma, P. J., Chowdhury, J. R., Huang, T. J., Lahiri, P., Elferink, R. P., Van Es, H. H., et al. (1992b). Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-najjar syndrome, type I. FASEB J 6:2859–2863.
  • Bosma, P. J., Chowdhury, N. R., Goldhoorn, B. G., Hofker, M. H., Oude Elferink, R. P., Jansen, P. L., et al. (1992a). Sequence of exons and the flanking regions of human bilirubin-UDP-glucuronosyltransferase gene complex and identification of a genetic mutation in a patient with Crigler-najjar syndrome, type I. Hepatology 15:941–947.
  • Bosma, P. J., Goldhoorn, B., Oude Elferink, R. P., Sinaasappel, M., Oostra, B. A., Jansen, P. L. (1993). A mutation in bilirubin uridine 5’-diphosphate-glucuronosyltransferase isoform 1 causing Crigler-najjar syndrome type II [see comments]. Gastroenterology 105:216–220.
  • Bosma, P. J., Seppen, J., Goldhoorn, B., Bakker, C., Oude Elferink, R. P., Chowdhury, J. R., et al. (1994). Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man [published erratum appears in J Biol Chem 1994;269:2542]. J Biol Chem 269:17960–17964.
  • Campbell, S. D., de Morais, S. M., Xu, J. J. (2004). Inhibition of human organic anion transporting polypeptide OATP 1B1 as a mechanism of drug-induced hyperbilirubinemia. Chem Biol Interact 150:179–187.
  • Carlini, L. E., Meropol, N. J., Bever, J., Andria, M. L., Hill, T., Gold, P., et al. (2005). UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res 11:1226–1236.
  • Carulli, N., Ponz de Leon M., Mauro, E., Manenti, F., Ferrari, A. (1976). Alteration of drug metabolism in Gilbert’s syndrome. Gut 17:581–587.
  • Cecchin, E., Innocenti, F., D’Andrea, M., Corona, G., De Mattia, E., Biason, P., et al. (2009). Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants and their haplotypes on the outcome of metastatic colorectal cancer patients treated with fluorouracil, leucovorin, and irinotecan. J Clin Oncol 27:2457–2465.
  • Cheng, Z., Rios, G. R., King, C. D., Coffman, B. L., Green, M. D., Mojarrabi, B., et al. (1998). Glucuronidation of catechol estrogens by expressed human UDP-glucuronosyltransferases (UGTs) 1A1, 1A3, and 2B7. Toxicol Sci 45:52–57.
  • Chouinard, S., Tessier, M., Vernouillet, G., Gauthier, S., Labrie, F., Barbier, O., et al. (2005). Inactivation of the pure antiestrogen Fulvestrant and other synthetic estrogen molecules by UGT1A enzymes expressed in the breast tissue. Mol Pharmacol Epub Dec 8.
  • Ciotti, M., Basu, N., Brangi, M., Owens, I. S. (1999). Glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38) by the human UDP-glucuronosyltransferases encoded at the UGT1 locus. Biochem Biophys Res Commun 260:199–202.
  • Costa, E., Vieira, E., Martins, M., Saraiva, J., Cancela, E., Costa, M., et al. (2006). Analysis of the UDP-glucuronosyltransferase gene in Portuguese patients with a clinical diagnosis of Gilbert’s and Crigler-najjar syndromes. Blood Cells Mol Dis 36:91–97.
  • del Giudice, E. M., Perrotta, S., Nobili, B., Specchia, C., d’Urzo, G., Iolascon, A. (1999). Coinheritance of Gilbert’s syndrome increases the risk for developing gallstones in patients with hereditary spherocytosis. Blood 94:2259–2262.
  • Douillard, J. Y., Cunningham, D., Roth, A. D., Navarro, M., James, R. D., Karasek, P., et al. (2000). Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre, randomised trial. Lancet 355:1041–1047.
  • Duguay, Y., McGrath, M., Lepine, J., Gagne, J. F., Hankinson, S. E., Colditz, G. A., et al. (2004). The functional UGT1A1 promoter polymorphism decreases endometrial cancer risk. Cancer Res 64:1202–1207.
  • Ebner, T., Remmel, R. P., Burchell, B. (1993). Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. Mol Pharmacol 43:649–654.
  • Ehmer, U., Lankisch, T. O., Erichsen, T. J., Kalthoff, S., Freiberg, N., Wehmeier, M., et al. (2008). Rapid allelic discrimination by TaqMan PCR for the detection of the Gilbert’s syndrome marker, UGT1A1*28. J Mol Diagn 10:549–552.
  • Erps, L. T., Ritter, J. K., Hersh, J. H., Blossom, D., Martin, N. C., Owens, I. S. (1994). Identification of two single base substitutions in the UGT1 gene locus which abolish bilirubin uridine diphosphate glucuronosyltransferase activity in vitro. J Clin Invest 93:564–570.
  • Fang, J. L., Beland, F. A., Doerge, D. R., Wiener, D., Guillemette, C., Marques, M. M., et al. (2002). Characterization of benzo(a)pyrene-trans-7,8-dihydrodiol glucuronidation by human tissue microsomes and overexpressed UDP-glucuronosyltransferase enzymes. Cancer Res 62:1978–1986.
  • Fang, J. L., Lazarus, P. (2004). Correlation between the UDP-glucuronosyltransferase (UGT1A1) TATAA box polymorphism and carcinogen detoxification phenotype: significantly decreased glucuronidating activity against benzo(a)pyrene-7,8-dihydrodiol(-) in liver microsomes from subjects with the UGT1A1*28 variant. Cancer Epidemiol Biomark Prev 13:102–109.
  • Farheen, S., Sengupta, S., Santra, A., Pal, S., Dhali, G. K., Chakravorty, M., et al. (2006). Gilbert’s syndrome: high frequency of the (TA)7 TAA allele in India and its interaction with a novel CAT insertion in promoter of the gene for bilirubin UDP-glucuronosyltransferase 1 gene. World J Gastroenterol 12:2269–2275.
  • Folprecht, G., Kohne, C. H. (2004). The role of new agents in the treatment of colorectal cancer. Oncology 66:1–17.
  • Gagne, J. F., Montminy, V., Belanger, P., Journault, K., Gaucher, G., Guillemette, C. (2002). Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). Mol Pharmacol 62:608–617.
  • Gajdos, V., Petit, F. M., Perret, C., Mollet-Boudjemline, A., Colin, P., Capel, L., et al. (2006). Further evidence that the UGT1A1*28 allele is not associated with coronary heart disease: The ECTIM Study. Clin Chem 52:2313–2314.
  • Ghosal, A., Hapangama, N., Yuan, Y., Achanfuo-Yeboah, J., Iannucci, R., Chowdhury, S., et al. (2004). Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos 32:314–320.
  • Gilbert, A., Lereboullet, P. (1901). La cholamae simple familiale. [The simple hereditary cholestasis]. Sem Med 21:241–248.
  • Guillemette, C., De Vivo, I., Hankinson, S. E., Haiman, C. A., Spiegelman, D., Housman, D. E., et al. (2001). Association of genetic polymorphisms in UGT1A1 with breast cancer and plasma hormone levels. Cancer Epidemiol Biomark Prev 10:711–714.
  • Guillemette, C., Millikan, R. C., Newman, B., Housman, D. E. (2000a). Genetic polymorphisms in uridine-diphospho-glucuronosyltransferase 1A1 and association with breast cancer among African Americans. Cancer Res 60:950–956.
  • Guillemette, C., Ritter, J. K., Auyeung, D. J., Kessler, F. K., Housman, D. E. (2000b). Structural heterogeneity at the UDP-glucuronosyltransferase 1 locus: functional consequences of three novel missense mutations in the human UGT1A7 gene [in process citation]. Pharmacogenetics 10:629–644.
  • Haverfield, E. V., McKenzie, C. A., Forrester, T., Bouzekri, N., Harding, R., Serjeant, G., et al. (2005). UGT1A1 variation and gallstone formation in sickle cell disease. Blood 105:968–972.
  • Innocenti, F., Grimsley, C., Das, S., Ramirez, J., Cheng, C., Kuttab-Boulos, H., et al. (2002). Haplotype structure of the UDP-glucuronosyltransferase 1A1 promoter in different ethnic groups. Pharmacogenetics 12:725–733.
  • Innocenti, F., Ratain, M. J. (2003). Irinotecan treatment in cancer patients with UGT1A1 polymorphisms. Oncology (Williston Park) 17(5 Suppl 5):52–55.
  • Innocenti, F., Undevia, S. D., Iyer, L., Chen, P. X., Das, S., Kocherginsky, M., et al. (2004). Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 22:1382–1388. [Epub 2004 Mar 13].
  • Innocenti, F., Vokes, E. E., Ratain, M. J. (2006). Irinogenetics: what is the right star? J Clin Oncol 24:2221–2224.
  • Iyanagi, T. (1991). Molecular basis of multiple UDP-glucuronosyltransferase isoenzyme deficiencies in the hyperbilirubinemic rat (Gunn rat). J Biol Chem 266:24048–24052.
  • Iyer, L., King, C. D., Whitington, P. F., Green, M. D., Roy, S. K., Tephly, T. R., et al. (1998). Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. J Clin Invest 101:847–854.
  • Johnson, A. D., Kavousi, M., Smith, A. V., Chen, M. H., Dehghan, A., Aspelund, T., et al. (2009). Genomewide association meta-analysis for total serum bilirubin levels. Hum Mol Genet 18:2700–2710.
  • Kapitulnik, J. (2004). Bilirubin: an endogenous product of heme degradation with both cytotoxic and cytoprotective properties. Mol Pharmacol 66:773–779.
  • Katoh, M., Yoshioka, Y., Nakagawa, N., Yokoi, T. (2009). Effects of Japanese herbal medicine, Kampo, on human UGT1A1 activity. Drug Metab Pharmacokinet 24(3):226–234.
  • Kawato, Y., Aonuma, M., Hirota, Y., Kuga, H., Sato, K. (1991). Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res 51:4187–4191.
  • King, C. D., Green, M. D., Rios, G. R., Coffman, B. L., Owens, I. S., Bishop, W. P., et al. (1996). The glucuronidation of exogenous and endogenous compounds by stably expressed rat and human UDP-glucuronosyltransferase 1.1. Arch Biochem Biophys 332:92–100.
  • King, C. D., Rios, G. R., Green, M. D., MacKenzie, P. I., Tephly, T. R. (1997). Comparison of stably expressed rat UGT1.1 and UGT2B1 in the glucuronidation of opioid compounds. Drug Metab Dispos 25:251–255.
  • Kohle, C., Mohrle, B., Munzel, P. A., Schwab, M., Wernet, D., Badary, O. A., et al. (2003). Frequent co-occurrence of the TATA box mutation associated with Gilbert’s syndrome (UGT1A1*28) with other polymorphisms of the UDP-glucuronosyltransferase-1 locus (UGT1A6*2 and UGT1A7*3) in Caucasians and Egyptians. Biochem Pharmacol 65:1521–1527.
  • Kuehl, G. E., Lampe, J. W., Potter, J. D., Bigler, J. (2005). Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos 33:1027–1035.
  • Labrune, P., Myara, A., Hadchouel, M., Ronchi, F., Bernard, O., Trivin, F., et al. (1994). Genetic heterogeneity of Crigler-najjar syndrome type I: a study of 14 cases. Hum Genet 94:693–697.
  • Lampe, J. W., Bigler, J., Horner, N. K., Potter, J. D. (1999). UDP-glucuronosyltransferase (UGT1A1*28 and UGT1A6*2) polymorphisms in Caucasians and Asians: relationships to serum bilirubin concentrations. Pharmacogenetics 9:341–349.
  • Lankisch, T. O., Behrens, G., Ehmer, U., Mobius, U., Rockstroh, J., Wehmeier, M., et al. (2009). Gilbert’s syndrome and hyperbilirubinemia in protease inhibitor therapy—an extended haplotype of genetic variants increases risk in indinavir treatment. J Hepatol 50:1010–1018.
  • Lankisch, T. O., Moebius, U., Wehmeier, M., Behrens, G., Manns, M. P., Schmidt, R. E., et al. (2006). Gilbert’s disease and atazanavir: from phenotype to UDP-glucuronosyltransferase haplotype. Hepatology 44:1324–1332.
  • Lankisch, T. O., Schulz, C., Zwingers, T., Erichsen, T. J., Manns, M. P., Heinemann, V., et al. (2008). Gilbert’s syndrome and irinotecan toxicity: combination with UDP-glucuronosyltransferase 1A7 variants increases risk. Cancer Epidemiol Biomark Prev 17:695–701.
  • Lankisch, T. O., Vogel, A., Eilermann, S., Fiebeler, A., Krone, B., Barut, A., et al. (2005). Identification and characterization of a functional TATA box polymorphism of the UDP glucuronosyltransferase 1A7 gene. Mol Pharmacol 67:1732–1739.
  • Lin, J. P., O’Donnell, C. J., Schwaiger, J. P., Cupples, L. A., Lingenhel, A., Hunt, S. C., et al. (2006). Association between the UGT1A1*28 allele, bilirubin levels, and coronary heart disease in the Framingham Heart Study. Circulation 114:1476–1481.
  • Lin, J. P., Schwaiger, J. P., Cupples, L. A., O’Donnell, C. J., Zheng, G., Schoenborn, V., et al. (2009). Conditional linkage and genomewide association studies identify UGT1A1 as a major gene for antiatherogenic serum bilirubin levels—the Framingham Heart Study. Atherosclerosis Epub Mar 19.
  • Macklon, A. F., Savage, R. L., Rawlins, M. D. (1979). Gilbert’s syndrome and drug metabolism. Clin Pharmacokinet 4:223–232.
  • Maitland, M. L., Grimsley, C., Kuttab-Boulos, H., Witonsky, D., Kasza, K. E., Yang, L., et al. (2006). Comparative genomics analysis of human sequence variation in the UGT1A gene cluster. Pharmacogenomics J 6:52–62.
  • Marcuello, E., Altes, A., Menoyo, A., Del Rio E., Gomez-Pardo, M., Baiget, M. (2004). UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer. Br J Cancer 91:678–682.
  • Martin, J. F., Vierling, J. M., Wolkoff, A. W., Scharschmidt, B. F., Vergalla, J., Waggoner, J. G., et al. (1976). Abnormal hepatic transport of indocyanine green in Gilbert’s syndrome. Gastroenterology 70:385–391.
  • McGrath, M., Lepine, J., Lee, I. M., Villeneuve, L., Buring, J., Guillemette, C., et al. (2009). Genetic variations in UGT1A1 and UGT2B7 and endometrial cancer risk. Pharmacogenet Genom 19:239–243.
  • Moghrabi, N., Clarke, D. J., Boxer, M., Burchell, B. (1993a). Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-najjar syndrome type 2. Genomics 18:171–173.
  • Moghrabi, N., Clarke, D. J., Burchell, B., Boxer, M. (1993b). Cosegregation of intragenic markers with a novel mutation that causes Crigler-Najjar syndrome type I: implication in carrier detection and prenatal diagnosis. Am J Hum Genet 53:722–729.
  • Monaghan, G., Ryan, M., Seddon, R., Hume, R., Burchell, B. (1996). Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert’s syndrome. Lancet 347:578–581.
  • Nguyen, N., Bonzo, J. A., Chen, S., Chouinard, S., Kelner, M. J., Hardiman, G., et al. (2008). Disruption of the UGT1 locus in mice resembles human Crigler-najjar type I disease. J Biol Chem 283:7901–7911.
  • Ogilvie, B. W., Zhang, D., Li, W., Rodrigues, A. D., Gipson, A. E., Holsapple, J., et al. (2006). Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor of cyp2c8: implications for drug-drug interactions. Drug Metab Dispos 34:191–197.
  • Onoue, M., Terada, T., Kobayashi, M., Katsura, T., Matsumoto, S., Yanagihara, K., et al. (2009). UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients. Int J Clin Oncol 14:136–142.
  • Palomaki, G. E., Bradley, L. A., Douglas, M. P., Kolor, K., Dotson, W. D. (2009). Can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? An evidence-based review. Genet Med 11:21–34.
  • Prueksaritanont, T., Subramanian, R., Fang, X., Ma, B., Qiu, Y., Lin, J. H., et al. (2002). Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab Dispos 30:505–512.
  • Rantner, B., Kollerits, B., Anderwald-Stadler, M., Klein-Weigel, P., Gruber, I., Gehringer, A., et al. (2008). Association between the UGT1A1 TA-repeat polymorphism and bilirubin concentration in patients with intermittent claudication: results from the CAVASIC study. Clin Chem 54:851–857.
  • Ribrag, V., Koscielny, S., Casasnovas, O., Cazeneuve, C., Brice, P., Morschhauser, F., et al. (2009). Pharmacogenetic study in Hodgkin lymphomas reveals the impact of UGT1A1 polymorphisms on patient prognosis. Blood 113:3307–3313.
  • Rigato, I., Ostrow, J. D., Tiribelli, C. (2005). Bilirubin and the risk of common nonhepatic diseases. Trends Mol Med 11:277–283.
  • Ritter, J. K., Chen, F., Sheen, Y. Y., Tran, H. M., Kimura, S., Yeatman, M. T., et al. (1992a). A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini. J Biol Chem 267:3257–3261.
  • Ritter, J. K., Crawford, J. M., Owens, I. S. (1991). Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells. J Biol Chem 266:1043–1047.
  • Ritter, J. K., Yeatman, M. T., Ferreira, P., Owens, I. S. (1992b). Identification of a genetic alteration in the code for bilirubin UDP-glucuronosyltransferase in the UGT1 gene complex of a Crigler-najjar type I patient. J Clin Invest 90:150–155.
  • Ritter, J. K., Yeatman, M. T., Kaiser, C., Gridelli, B., Owens, I. S. (1993). A phenylalanine codon deletion at the UGT1 gene complex locus of a Crigler-najjar type I patient generates a pH-sensitive bilirubin UDP- glucuronosyltransferase. J Biol Chem 268:23573–23579.
  • Rotger, M., Taffe, P., Bleiber, G., Gunthard, H. F., Furrer, H., Vernazza, P., et al. (2005). Gilbert’s syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia. J Infect Dis 192:1381–1386.
  • Rouits, E., Boisdron-Celle, M., Dumont, A., Guerin, O., Morel, A., Gamelin, E. (2004). Relevance of different UGT1A1 polymorphisms in irinotecan-induced toxicity: a molecular and clinical study of 75 patients. Clin Cancer Res 10:5151–5159.
  • Sai, K., Saeki, M., Saito, Y., Ozawa, S., Katori, N., Jinno, H., et al. (2004). UGT1A1 haplotypes associated with reduced glucuronidation and increased serum bilirubin in irinotecan-;administered Japanese patients with cancer. Clin Pharmacol Ther 75:501–515.
  • Saracino, M. R., Bigler, J., Schwarz, Y., Chang, J. L., Li, S., Li, L., et al. (2009). Citrus fruit intake is associated with lower serum bilirubin concentration among women with the UGT1A1*28 polymorphism. J Nutr 139:555–560.
  • Schwertner, H. A., Vitek, L. (2008). Gilbert syndrome, UGT1A1*28 allele, and cardiovascular disease risk: possible protective effects and therapeutic applications of bilirubin. Atherosclerosis 198:1–11.
  • Seppen, J., Bosma, P. J., Goldhoorn, B. G., Bakker, C. T., Chowdhury, J. R., Chowdhury, N. R., et al. (1994). Discrimination between Crigler-najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase. J Clin Invest 94:2385–2391.
  • Siow, R. C., Sato, H., Mann, G. E. (1999). Heme oxygenase-carbon monoxide signalling pathway in atherosclerosis: antiatherogenic actions of bilirubin and carbon monoxide? Cardiovasc Res 41:385–394.
  • Sparks, R., Ulrich, C. M., Bigler, J., Tworoger, S. S., Yasui, Y., Rajan, K. B., et al. (2004). UDP-glucuronosyltransferase and sulfotransferase polymorphisms, sex hormone concentrations, and tumor receptor status in breast cancer patients. Breast Cancer Res 6:R488–R498.
  • Stewart, C. F., Panetta, J. C., O’Shaughnessy, M. A., Throm, S. L., Fraga, C. H., Owens, T., et al. (2007). UGT1A1 promoter genotype correlates with SN-38 pharmacokinetics, but not severe toxicity in patients receiving low-dose irinotecan. J Clin Oncol 25:2594–2600.
  • Strassburg, C. P. (2008). Pharmacogenetics of Gilbert’s syndrome. Pharmacogenomics 9:903–915.
  • Strassburg, C. P., Kalthoff, S., Ehmer, U. (2008). Variability and function of family 1 uridine-5’-diphosphate glucuronosyltransferases (UGT1A). Crit Rev Clin Lab Sci 45:485–530.
  • Strassburg, C. P., Manns, M. P. (2000). Jaundice, genes, and promoters. J Hepatol 33:476–479.
  • Strassburg, C. P., Vogel, A., Kneip, S., Tukey, R. H., Manns, M. P. (2002). Polymorphisms of the UDP-glucuronosyltransferase (UGT) 1A7 gene in colorectal cancer. Gut 50:851–856.
  • Sugatani, J., Yamakawa, K., Yoshinari, K., Machida, T., Takagi, H., Mori, M., et al. (2002). Identification of a defect in the UGT1A1 gene promoter and its association with hyperbilirubinemia. Biochem Biophys Res Commun 292:492–497.
  • Sutomo, R., Laosombat, V., Sadewa, A. H., Yokoyama, N., Nakamura, H., Matsuo, M., et al. (2002). Novel missense mutation of the UGT1A1 gene in Thai siblings with Gilbert’s syndrome. Pediatr Int 44:427–432.
  • Tallman, M. N., Miles, K., Kessler, F., Neilson, J., Tian, X., Ritter, J. K., et al. (2006). The contribution of intestinal UDP-glucuronosyltrasferases in modulating Sn-38 induced gastrointestinal toxicity in rats. J Pharmacol Exp Ther Epub Sep 26.
  • Tang, K. S., Chiu, H. F., Chen, H. H., Eng, H. L., Tsai, C. J., Teng, H. C., et al. (2005). Link between colorectal cancer and polymorphisms in the uridine-diphosphoglucuronosyltransferase 1A7 and 1A1 genes. World J Gastroenterol 11:3250–3254.
  • Testa, R., Bardellini, E., Borzone, S., Montani, P., Risso, D., Bindi, P., et al. (1995). Caffeine clearance in subjects with constitutional unconjugated hyperbilirubinemia. Ital J Gastroenterol 27:129–132.
  • Thomas, S. S., Li, S. S., Lampe, J. W., Potter, J. D., Bigler, J. (2006). Genetic variability, haplotypes, and htSNPs for exons 1 at the human UGT1A locus. Hum Mutat 27:717.
  • Tukey, R. H., Strassburg, C. P. (2000). Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 40:581–616.
  • Tukey, R. H., Strassburg, C. P., Mackenzie, P. I. (2002). Pharmacogenomics of human UDP-glucuronosyltransferases and irinotecan toxicity. Mol Pharmacol 62:446–450.
  • Udomuksorn, W., Elliot, D. J., Lewis, B. C., Mackenzie, P. I., Yoovathaworn, K., Miners, J. O. (2007). Influence of mutations associated with Gilbert’s and Crigler-najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates. Pharmacogenet Genom 17:1017–1029.
  • Vasavda, N., Menzel, S., Kondaveeti, S., Maytham, E., Awogbade, M., Bannister, S., et al. (2007). The linear effects of alpha-;thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease. Br J Haematol 138:263–270.
  • Vera, T., Granger, J. P., Stec, D. E. (2009). Inhibition of bilirubin metabolism induces moderate hyperbilirubinemia and attenuates angiotensin-II–dependent hypertension in mice. Am J Physiol Regul Integr Comp Physiol Epub Jul 1.
  • Wasmuth, H. E., Keppeler, H., Herrmann, U., Schirin-Sokhan, R., Barker, M., Lammert, F. (2006). Coinheritance of Gilbert syndrome-associated UGT1A1 mutation increases gallstone risk in cystic fibrosis. Hepatology 43:738–741.
  • Zhang, D., Chando, T. J., Everett, D. W., Patten, C. J., Dehal, S. S., Humphreys, W. G. (2005). In vitro inhibition of UDP-glucuronosyltransferases by atazanavir and other HIV protease inhibitors and the relationship of this property to in vivo bilirubin glucuronidation. Drug Metab Dispos 33:1729–1739.
  • Zucker, S. D., Qin, X., Rouster, S. D., Yu, F., Green, R. M., Keshavan, P., et al. (2001). Mechanism of indinavir-induced hyperbilirubinemia. Proc Natl Acad Sci U S A 98:12671–12676.

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