Pharmacogenetics of Gilbert's syndrome

Pharmacogenomics

Volumn 9, Issue 6, 2008, Pages 703-715

  Strassburg, Christian P ^a  

^a HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

Atazanavir; Drug toxicity; Genotyping; Gilbert's syndrome; Haplotype; Irinotecan; Pharmacogenetic risk; Promoter; Single nucleotide polymorphisms; SNP; UGT1A1

Indexed keywords

7 ETHYL 10 HYDROXYCAMPTOTHECIN; ATAZANAVIR; ATORVASTATIN; BILIRUBIN; BUPRENORPHINE; CERIVASTATIN; ETHINYLESTRADIOL; EZETIMIBE; FULVESTRANT; GEMFIBROZIL; GLUCURONOSYLTRANSFERASE 1A1; GLUCURONOSYLTRANSFERASE 1A10; GLUCURONOSYLTRANSFERASE 1A3; GLUCURONOSYLTRANSFERASE 1A6; GLUCURONOSYLTRANSFERASE 1A7; GLUCURONOSYLTRANSFERASE 1A8; GLUCURONOSYLTRANSFERASE 1A9; IBUPROFEN; INDINAVIR; IRINOTECAN; KETOPROFEN; SIMVASTATIN; DRUG; GLUCURONOSYLTRANSFERASE; PHENOL GLUCURONOSYLTRANSFERASE;

BONE MARROW SUPPRESSION; BREAST CANCER; CANCER RISK; CAUCASIAN; COLORECTAL CANCER; DIARRHEA; DRUG DOSE REDUCTION; DRUG ELIMINATION; DRUG GLUCURONIDATION; DRUG RESEARCH; DRUG SAFETY; EXON; GASTROINTESTINAL DISEASE; GASTROINTESTINAL TRACT; GENE EXPRESSION; GENE LOCUS; GENETIC LINKAGE; GENETIC VARIABILITY; GILBERT DISEASE; GLUCURONIDATION; HAPLOTYPE; HEPATITIS; HUMAN; HYPERBILIRUBINEMIA; INDIVIDUALIZATION; INTRON; JAUNDICE; LEUKOPENIA; LIVER DISEASE; LIVER FAILURE; LIVER FIBROSIS; NEUTROPENIA; NONHUMAN; OVARY CANCER; PATIENT CARE; PHARMACOGENETICS; PREDICTION; PROMOTER REGION; REVIEW; THROMBOCYTOPENIA; ANIMAL; DRUG TOXICITY; ENZYMOLOGY; GENETICS; METABOLISM; NEOPLASM;

ANIMALS; BILIRUBIN; DRUG TOXICITY; GILBERT DISEASE; GLUCURONOSYLTRANSFERASE; HUMANS; NEOPLASMS; PHARMACEUTICAL PREPARATIONS; PHARMACOGENETICS; VARIATION (GENETICS);

EID: 48949119333     PISSN: 14622416     EISSN: 17448042     Source Type: Journal    
DOI: 10.2217/14622416.9.6.703     Document Type: Review

References (92)

1. Gilbert A, Lereboullet P: La cholamae simple familiale. Sem. Med. 21, 241-248 (1901).
2. Arias IM: Chronic unconjugated hyperbilirubinemia without signs of overt hemolysis in adolescents and adults. J. Clin. Invest. 41, 2233-2245 (1962).
3. Strassburg CP, Manns MP: Jaundice, genes and promoters. J. Hepatol. 33, 476-479 (2000).
4. Bosma PJ, Chowdhury JR, Bakker C et al.: The genetic basis of the reduced expression of bilirubin UDP- glucuronosyltransferase 1 in Gilbert's syndrome. N. Engl. J. Med. 333(18), 1171-1175 (1995).
5. Novotny L, Vitek L: Inverse relationship between serum bilirubin and atherosclerosis in men: a meta-analysis of published studies. Exp. Biol. Med. (Maywood) 228(5), 568-571 (2003).
6. Stow RC, Sato H, Mann GE: Heme oxygenase-carbon monoxide signalling pathway in atherosclerosis: anti-atherogenic actions of bilirubin and carbon monoxide? Cardiovasc. Res. 41(2), 385-394 (1999).
7. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN: Bilirubin is an antioxidant of possible physiological importance. Science 235(4792), 1043-1046 (1987).
8. Lankisch TO, Moebius U, Wehmeier M et al.: Gilbert's disease and atazanavir: from phenotype to UDP-glucuronosyltransferase haplotype. Hepatology 44(5), 1324-1332 (2006).
9. Costa E: Hematologically important mutations: bilirubin UDP-glucuronosyltransferase gene mutations in Gilbert and Crigler-Najjar syndromes. Blood Cells Mol. Dis. 36(1), 77-80 (2006).
10. Hirschfield GM, Alexander GJ: Gilbert's syndrome: an overview for clinical biochemists. Ann. Clin. Biochem. 3(Pt 5), 340-343 (2006).
11. Huang CS: Molecular genetics of unconjugated hyperbilirubinemia in Taiwanese. J. Biomed. Sci. 12(3), 445-450 (2005).
12. Gong QH, Cho JW, Huang T et al.: Thirteen UDP glucuronosyltransferase genes are encoded at the human UGT1 gene complex locus. Pharmacogenetics 11(4), 357-368 (2001).
13. Tukey RH, Strassburg CP: Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu. Rev. Pharmacol. Toxicol. 40, 581-616 (2000).
14. Tukey RH, Strassburg CP: Genetic Multiplicity of the human UDP-glucuronosyltransferases and regulation in the gastrointestinal tract. Mol. Pharmacol. 59(3), 405-414 (2001).
15. Ritter JK, Chen F, Sheen YY et al.: A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini. J. Biol. Chem. 267(5), 3257-3261 (1992).
16. Strassburg CP, Kneip S, Topp J et al.: Polymorphic gene expression and interindividual variation of UDP-glucuronosyltransferase activity in human small intestine. J. Biol. Chem. 275, 36164-36171 (2000).
17. Strassburg CP, Manns MP, Tukey RH: Expression of the UDP-glucuronosyltransferase 1A locus in human colon. Identification and characterization of the novel extrahepatic UGT1A8. J. Biol. Chem. 273(15), 8719-8726 (1998).
18. Strassburg CP, Nguyen N, Manns MP, Tukey RH: Polymorphic expression of the UDP-glucuronosyltransferase UGT1A gene locus in human gastric epithelium. Mol. Pharmacol. 54(4), 647-654 (1998).
19. Strassburg CP, Nguyen N, Manns MP, Tukey RH: UDP-glucuronosyltransferase activity in human liver and colon. Gastroenterology 116(1), 149-160 (1999).
20. Strassburg CP, Oldhafer K, Manns MP, Tukey RH: Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue. Mol. Pharmacol. 52(2), 212-220 (1997).
21. Strassburg CP, Strassburg A, Nguyen N et al.: Regulation and function of family 1 and family 2 UDP-glucuronosyltransferase genes ( UGT1A, UGT2B) in human oesophagus. Biochem. J. 338(Pt 2). 489-498 (1999).
22. Strassburg CP, Strassburg A, Kneip S et al.: Developmental aspecis of human hepatic drug glucuronidation in young children and adults. Gut 50, 259-265 (2002).
23. Ehmer U, Vogel A, Schutte JK et al.: Variation of hepatic glucuronidation: novel functional polymorphisms of the UDP-glucuronosyltransferase UGT1A4. Hepatology 39(4), 970-977 (2004).
24. Kohle C, Mohrle B, Munzel PA et al.: 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) Caucasians and Egyptians. Biochem. Pharmacol. 65(9), 1521-1527 (2003).
25. Lampe JW, Bigler J, Horner NK, Potter JD: UDP-glucuronosyltransferase (UGT1A1*28 and UGT1A6*2) polymorphisms in Caucasians and Asians: relationships to serum bilirubin concentrations. Pharmacogenetics 9(3), 341-349 (1999).
26. Lankisch TO, Vogel A, Eilermann S et al.: Identification and characterization of a functional TATA box polymorphism of the UDP glucuronosyltransferase 1A7 gene. Mol. Pharmacol. 67(5), 1732-1739 (2005).
27. Guillemerte C, Ritter JK, Auyeung DJ, Kessler FK, Housman DE: Structural heterogeneity at the UDP- glucuronosyltransferase 1 locus: functional consequences of three novel missense mutations in the human UGT1A7 gene. Pharmacogenetics 10(7), 629-644 (2000).
28. Strassburg CP, Vogel A, Kneip S, Tukey RH, Manns MP: Polymorphisms of the UDP-glucuronosyltransferase (UFT) 1A7 gene in colorectal cancer. Gut 50, 851-856 (2002).
29. Erichsen TJ, Ehmer U, Kalthoff S et al.: Genetic variability of aryl hydrocarbon receptor (AhR)-mediated regulation of the human UDP glucuronosyltransferase (UGT) 1A4 gene. Toxicol. Appl. Pharmacol. dol:10.1016/j.taap.2008.02.02024 (2008) (Epub ahead of print).
30. Ritter JK, Crawford JM, Owens IS: Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells. J Biol. Chem. 266(2), 1043-1047 (1991).
31. Bosma PJ, Chowdhury JR, Huang TJ et al.: Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome. Type I. FASEB J. 6(10). 2859-2863 (1992).
32. Bosma PJ, Chowdhury NR, Goldhoorn BG et al.: 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(5), 941-947 (1992).
33. Iyanagi T: Molecular basis of multiple UDP-glucuronosyltransferase isoenzyme deficiencies in the hyperbilirubinemic rat (Gunn rat). J. Biol. Chem. 266(35), 24048-24052 (1991).
34. Bosma PJ, Goldhoorn B, Oude Elferink RP et al.: A mutation in bilirubin uridine 5′-diphosphate-glucuronosyltransferase isoform 1 causing Crigler-Najjar syndrome. Type II. Gastroenterology 105(1), 216-220 (1993).
35. Ritter JK, Yeatman MT, Kaiser C, Gridelli B, Owens IS: 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(31), 23573-23579 (1993).
36. Bosma PJ, Seppen J, Goldhoorn B et al.: Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. J. Biol. Chem. 269(27), 17960-17964 (1994).
37. Lankisch TO, Schulz C, Zuvingers T et al.: Gilbert's syndrome and irinotecan toxicity: combination with UDP- glucuronosyltransferase 1A7 variants increases risk. Cancer Epidemiol. Biomarkers Prev. 17(3). 695-701 (2008).
38. Fang JL, Lazarus P: 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 live microsomes from subjects with the UCT1A1*28 variant. Cancer Epidermiol. Biomarkers Prev. 13(1), 102-109 (2004).
39. Monaghan G. Ryan M. Seddon R. Hume R. Burchett B: Genetic variation iii bilirubin UPD glucuronosyltransferase gene promoter and Gilbert's syndrome. Lancet 347(9001). 578-581 (1996).
40. Balram C, Sabapathy K, Fei G, Khoo KS, Lee EJ: Genetic polymorphisms of UDP-glucuronosyltransferase in Asians: UGT1A1*28 is a common allele in Indians. Pharmacogenetics 12(1), 81-83 (2002).
41. Beuder E, Gelbart T. Demina A: Racial variability in the UDP-glucuronosyltransferase I (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc. Natl Acad. Sci. USA 95(14), 8170-8174 (1998).
42. Ando Y, Chida M, Nakayama K, Saka H, Kamataki T. The UGT1A1*28 allele is relatively rare in a Japanese population. Pharmacogenetics 8(4), 357-360 (1998).
43. Aono S, Yamada Y, Keino H et al.: 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(3), 1239-1244 (1993).
44. Anon S, Adachi Y. Uyama E et al.: Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert's syndrome. Lancet 345(8955), 958-959 (1995).
45. Udomuksorn W, Elliot DJ, Lewis BC et al.: Influence of mutations associated with Gilbert and Crigler-Najjar Type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates. Pharmacogenet. Genomics 17 (12), 1017-1029 (2007).
46. Sugatani J, Yamakawa K, Yoshinari K et al.: Identification of a defect in the UGT1A1 gene promoter and its association with hyperbilirubinemia. Biochem. Biophys. Res. Commun. 292(2), 492-497 (2002).
47. Costa E, Vieira E, Martins M et al.: Analysis of the UDP-glucuronosyltransferase gene in Portuguese patients with a clinical diagnosis of Gilbert and Crigler-Najjar syndromes. Blood Cells Mol. Dis. 36(1), 91-97 (2006).
48. Farheen S. Sengupta S, Santra A et al.: 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(14), 2269-2275 (2006).
49. Sai K, Saeki M, Saito Y et al.: UCT1A1 haplotypes associated with reduced glucuronidation and increased serum bilirubin in irinotecan-administered Japanese patients with cancer. Clin. Pharmacol. Ther. 75(6), 501-515 (2004).
50. Innocenti F. Grimsley C, Das S et al.: Haplotype structure of the UDP-glucuronosyltransferase 1A1 promoter in different ethnic groups. Pharmacogenetics 12(9), 725-733 (2002).
51. Cheng Z, Rios GR, King CD et al.: Glucuronidation of catechol estrogens by expressed human UDP-glucuronosyltransferases (UGTs) 1A1, 1A3, and 2137. Toxicol. Sci. 45(1), 52-57 (1998).
52. Fang JL, Beland FA, Doerge DR et al.: Characterization of benzo(a)pyrene-trans7, 8-dihydrodiol glucuronidation by human tissue microsomes and overexpressed UDP-glucuronosyltransferase enzymes. Cancer Res. 62(7), 1978-1986 (2002).
53. Tang KS, Chiu HE Chen HH et al.: Link between colorectal cancer and polymorphisms in the uridine-diphosphoglocuronosyl transferase 1A7 and 1AI genes. World J. Gastroenterol. 11(21), 3250-3254(2005).
54. Guillemettet Millikan RC. Newman B. Housman DE: Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and association with breast cancer among African Americans. Cancer Res. 60(4). 950-956-(2000).
55. Guillemette C De Vivo I, Hankinson SE et al.: Association of genetic polymorphisms in UGP1A1 with breast cancer and plasma hormone levels. Cancer Epidermiol. Biomarkers Prev. 11)(6), 711-714 (2001).
56. Sparks R, Ulrich CM, Bigler J et al.: UDP-glucuronosyltransferase and sulfotransferase polymorphisms, sex hormone concentrations, and tumor receptor status in breast cancer patients. Breast Cancer Res. 6(5), R488-R498 (2004).
57. Adegoke OJ, Sho XO, Gao YT et al.: Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) and risk of breast cancer. Breast Cancer Res. Treat. 85(3), 239-245 (2004).
58. Cecchin E, Russo A, Corona G et al.: UGT1A1*28 polymorphism in ovarian cancer patients. Oncol. Rep. 12(2), 457-462 (2004).
59. Chouinard S, Tessier M, Vernouillet G et al.: Inactivation of the pure antiestrogen Fulvestrant and other synthetic estrogen molecules by UGT1A enzymes expressed in the breast tissue. Mol. Pharmacol. 69(3), 908-920 (2006).
60. Ebner T, Remmel RP, Burchell B: Human bilirubin UDP glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. Mol. Pharmacol. 43(4), 649-654 (1993).
61. Ghosal A, Hapangama N, Yuan Y et al.: Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetla). Drug Metab. Dispos. 32(3), 314-320 (2004).
62. King CD, Rios GR, Green MD, MacKenzie PI, Tephly TR: Comparison of stably expressed rat UGT1.1 and UGT2B1 in the glucuronidation of opioid compounds. Drug Metab. Dispos. 25(2), 251-255 (1997).
63. Kuehl GE, Lampe JW, Potter JD, Bigler J: Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab. Dispos. 33(7), 1027-1035 (2005).
64. Ogilvie BW, Zhang D, Li W et al.: Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor of CYP2C8: implications for drug-drug interactions. Drug Metab. Dispos. 34(1), 191-197 (2006).
65. Prueksaritanont T, Subramanian R, Fang X et al.: Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab. Dispos. 30(5), 505-512 (2002).
66. Innocenti F, Vokes EE, Ratain MJ: Irinogenetics: what is the right star? J. Clin. Oncol. 24(15), 2221-2224 (2006).
67. Ando Y, Saka H, Asai G et al: UGT1.A1 genotypes and glucuronidation of SN-38, the active metabolite of irinotecan. Ann. Oncol. 9(8), 845-847 (1998).
68. Douiliard JY, Cunningham D, Roth AD et al.: Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355(9209), 1041-1047 (2000).
69. Folprecht G. Kohne CH: The role of new agents in the treatment of colorectal cancer. Oncology 66(1), 1-17 (2004).
70. Kawato Y, Aonuma M. Hirota Y, Kuga H, Sato K: Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res. 51(16), 4187-4191 (1991).
71. Tukey RH, Strassburg CP, Mackenzie PI: Pharmacogenomics of human UDP glucuronosyltransferases and irinotecan toxicity. Mol. Pharmacol. 62(3), 446-450 (2002).
72. Innocenti F. Ratain MJ: Irinotecan treatment in cancer patients with UGT1A1 polymorphisms. Oncology (Williston Park) 17(5 Suppl. 5), 52-55 (2003).
73. Gagne JF, Montminy V, Belanger P et al.: Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). Mol. Pharmacol. 62(3), 608-617 (2002).
74. Innocenti F, Undevia SD, Iyer L et al.: Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J. Clin. Oncol. 22(8), 1382-1388 (2004).
75. Iyer L, King CD, Whitington PF et al.: 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(4), 847-854 (1998).
76. Marcuello E, Altes A, Menoyo, A et al.: UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer. Br. J. Cancer 91(4), 678-692 (2004).
77. Rouits E. Boisdron-Celle M. Dumont A et al.: Relevance of different UGT1A1 polymorphisms in irinotecan-induced toxicity: a molecular and clinical study, of 75 patients. Clin. Cancer Res. 10(15), 5151-5159 (2004).
78. Carlini LE, Meropol NJ, Bever J et al: UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin. Cancer Res. 11(3), 1226-1236 (2005).
79. Ciotti M, Basu N, Brangi M, Owens IS: Glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38) by the human UDP-glucuronosyltransferases encoded at the UGT1 locus. Biochem. Biophys. Res. Commun. 260(1), 199-202 (1999).
80. Tallman MN, Miles K, Kessler F et al.: The contribution of intestinal UDP-glucuronosyltrasferases in modulating sn-38 induced gastrointestinal toxicity in rats. J. Pharmacol. Exp. Ther. 320(1), 29-37 (2006).
81. Rotger M, Taffe P, Bleiber G et al.: Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia. J. Infect. Dis. 192(8), 1381-1386 (2005).
82. Zhang D, Chando TJ, Everett DW et al.: 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(11), 1729-1739 (2005).
83. Emi Y, Ikushiro S, Iyanagi T: Xenobiotic responsive element-mediated transcriptional activation in the UDP-glucuronosyltransferase family 1 gene complex. J. Biol. Chem. 271(7), 3952-3958 (1996).
84. Ritter JK, Kessler FK, Thompson MT et al.: Expression and inducibility of the human bilirubin UDP-glucuronosyltransferase UGT1A1 in liver and cultured primary hepatocytes: evidence for both genetic and environmental influences. Hepatology 30(2), 476-484 (1999).
85. Usui T, Kuno T, Ueyama H, Ohkubo I, Mizutani T: Proximal HNF1 element is essential for the induction of human UDP-glucuronosyltransferase 1A1 by glucocorticoid receptor. Biochem. Pharmacol. 71(5), 693-701 (2005).
86. Yueh MF, Tukey RH: Nrf2-Keap1 signaling pathway regulates human UGT1A1 expression in vitro and in transgenic UGT1 mice. J. Biol. Chem. 282(12), 8749-8758 (2007).
87. Sugatani J, Kojima H, Ueda A et al.: The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. Hepatology 33(5), 1232-1238 (2001).
88. Ellis E, Wagner M, Lammert F et al.: Successful treatment of severe unconjugated hyperbilirubinemia via induction of UGT1A1 by rifampicin. J. Hepatol. 44(1), 243-245 (2006).
89. Macklon AF, Savage RL, Rawlins MD: Gilbert's syndrome and drug metabolism. Clin. Pharmacokinet. 4(3), 223-232 (1979).
90. Martin JF, Vierling JM, Wolkoff AW et al.: Abnormal hepatic transport of indocyanine green in Gilbert's syndrome. Gastroenterology 70(3), 385-391 (1976).
91. King CD, Green MD, Rios GR et al.: The glucuronidation of exogenous and endogenous compounds, by stably expressed rat and human UDP-glucuronosyltransferase 1.1. Arch. Biochem. Biophys. 332(1), 92-100 (1996).
92. Sutomo R, Laosombat V, Sadewa AH et al.: Novel missense mutation of the UGT1A1 gene in Thai siblings with Gilbert's syndrome. Pediatr. Int. 44(4), 427-432 (2002).