Exploring the genetic architecture of neonatal hyperbilirubinemia

Seminars in Fetal and Neonatal Medicine

Volumn 15, Issue 3, 2010, Pages 169-175

  Watchko, Jon F ^a   Lin, Zhili ^b  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b PERKINELMER INC   (United States)

Author keywords

Compound heterozygosity; Genetics; Glucose 6 phosphate dehydrogenase (G6PD); Hyperbilirubinemia; Solute carrier organic anion transporter polypeptide 1B1 (SLCO1B1); Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1)

Indexed keywords

BILIRUBIN; BILIVERDIN REDUCTASE A; GLUCOSE 6 PHOSPHATE DEHYDROGENASE; GLUCURONOSYLTRANSFERASE 1A1; HEME OXYGENASE 1; ORGANIC ANION TRANSPORTER 2; OXIDOREDUCTASE; UNCLASSIFIED DRUG;

ARTICLE; ETHNICITY; FAMILY HISTORY; GENE MUTATION; GENETIC POLYMORPHISM; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOTYPE; GILBERT DISEASE; HETEROZYGOSITY; HUMAN; NEWBORN JAUNDICE; RISK FACTOR; SEX DIFFERENCE; TWINS;

FEMALE; GENETIC VARIATION; GLUCOSEPHOSPHATE DEHYDROGENASE; GLUCURONOSYLTRANSFERASE; HUMANS; HYPERBILIRUBINEMIA, NEONATAL; INFANT, NEWBORN; MALE; ORGANIC ANION TRANSPORTERS; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 77953289852     PISSN: 1744165X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.siny.2009.11.003     Document Type: Article

References (110)

1. Watchko J.F. Indirect hyperbilirubinemia in the neonate. In: Maisels M.J., and Watchko J. (Eds). Neonatal jaundice (2000), Harwood, Amsterdam 51-66
2. Maisels M.J., and Kring E. Length of stay, jaundice and hospital readmission. Pediatrics 101 (1998) 995-998
3. Bhutani V.K., Johnson L.H., Maisels M.J., et al. Kernicterus: epidemiological strategies for its prevention through systems-based approaches. J Perinatol 24 (2004) 650-662
4. Johnson L., Bhutani V.K., Karp K., Sivieri E.M., and Shapiro S.M. Clinical report from the Pilot USA Kernicterus Registry (1992 to 2004). J Perinatol 29 (2009) S25-S45
5. Perlstein M.A. The late clinical syndrome of posticteric encephalopathy. Pediatr Clin North Am 7 (1960) 665-687
6. Watchko J.F., Daood M.J., and Biniwale M. Understanding neonatal hyperbilirubinemia in the era of genomics. Semin Neonatol 7 (2002) 143-152
7. Watchko J.F. Vigintiphobia revisited. Pediatrics 115 (2005) 1747-1753
8. Kaplan M., and Hammerman C. Bilirubin and the genome: the hereditary basis of unconjugated neonatal hyperbilirubinemia. Curr Pharmacogenomics 3 (2005) 21-42
9. Bosma P.J. Inherited disorders of bilirubin metabolism. J Hepatol 38 (2003) 107-117
10. Kadakol A., Ghosh S.S., Sappal B.S., et al. Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype. Hum Mutat 16 (2000) 297-306
11. Kaplan M., Renbaum P., Levy-Lahad E., et al. Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia. Proc Natl Acad Sci U S A 94 (1997) 12128-12132
12. Beutler E. G6PD deficiency. Blood 84 (1994) 3613-3636
13. Huang C.S., Huang M.J., Lin M.S., et al. Genetic factors related to unconjugated hyperbilirubinemia amongst adults. Pharmacogenet Genomics 15 (2005) 43-50
14. Huang M.J., Kua K.E., Teng H.C., et al. Risk factors for severe hyperbilirubinemia in neonates. Pediatr Res 56 (2004) 682-689
15. Watchko J.F., Lin Z., Clark R.H., Kelleher A.S., Walker W., and Spitzer A.R. Complex multifactorial nature of significant hyperbilirubinemia in neonates. Pediatrics 124 (2009) e868-e877
16. Newman T.B., Escobar G.J., Gonzales V.M., Armstrong M.A., Gardner M.N., and Folck B.F. Frequency of neonatal bilirubin testing and hyperbilirubinemia in a large health maintenance organization. Pediatrics 104 (1999) 1198-1203
17. Kidd K.K., and Kidd J.R. Human genetic variation of medical significance. In: Stearns S.C., and Koella J.C. (Eds). Evolution in health and disease (2008), Oxford University Press, New York 51-62
18. Boomsma D., Busjahn A., and Peltonen L. Classical twin studies and beyond. Nat Rev Genet 3 (2002) 872-882
19. Ebbesen F., and Mortensen B.B. Difference in plasma bilirubin concentration between monozygotic and dizygotic newborn twins. Acta Paediatr 92 (2003) 569-573
20. Tan K.L. Neonatal jaundice in twins. Aust Paediatr J 16 (1980) 70-72
21. Dolan S.M., and Moore C. Linking family history in obstetric and pediatric care: assessing risk for genetic disease and birth defects. Pediatrics 120 (2007) S66-S70
22. Keren R., Luan X., Friedman S., et al. A comparison of alternative risk-assessment strategies for predicting significant neonatal hyperbilirubinemia in term and near term infants. Pediatrics 121 (2008) e170-e179
23. Gale R., Seidman D.S., Dollberg S., and Stevenson D.K. Epidemiology of neonatal jaundice in the Jerusalem population. J Pediatr Gastroenterol Nutr 10 (1990) 82-86
24. Newman T.B., Xiong B., Gonzales V.M., and Escobar G.J. Prediction and prevention of extreme neonatal hyperbilirubinemia in a mature health maintenance organization. Arch Pediatr Adolesc Med 154 (2000) 1140-1147
25. Khoury M.J., Calle E.E., and Joesoef R.M. Recurrence risk of neonatal hyperbilirubinemia in siblings. Am J Dis Child 142 (1988) 1065-1069
26. Nielsen H., Hasse P., Blaabjerg J., Stryhn H., and Hilden J. Risk factors and sib correlation in physiological neonatal jaundice. Acta Paediatr Scand 76 (1987) 504-511
27. Newman T.B., Easterling M.J., Goldman E.S., and Stevenson D.K. Laboratory evaluation of jaundice in newborns. Am J Dis Child 144 (1990) 364-368
28. American Academy of Pediatrics, and Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 114 (2004) 297-316
29. Ho N.K. Neonatal jaundice in Asia. Baillière's Clin Hematol 5 (1992) 131-142
30. Huang C.S., Luo G.A., Huang M.J., Yu S.C., and Yang S.S. Variations of the bilirubin uridine-glucuronosyl transferase 1A1 gene in healthy Taiwanese. Pharmacogenetics 10 (2000) 539-544
31. Huang C.S., Chang P.F., Huang M.J., et al. Relationship between bilirubin UDP-glucuronosyl transferase 1A1 gene and neonatal hyperbilirubinemia. Pediatr Res 52 (2002) 601-605
32. Yamamoto K., Sato H., Fujiyama Y., et al. Contribution of two missense mutations (G71R and Y486D) of the bilirubin UDP glycosyltransferase (UGT1A1) gene to phenotypes of Gilbert's syndrome and Crigler-Najjar syndrome type II. Biochim Biophys Acta 1406 (1998) 267-273
33. Gourley G.R. Disorders of bilirubin metabolism. In: Suchy F.J. (Ed). Liver disease in children (1994), Mosby-Yearbook, St Louis 401-413
34. Koiwai O., Nishizawa M., Hasada K., et al. Gilbert's syndrome is caused by a heterozygous missense mutation in the gene for bilirubin UDP-glucuronosyltransferase. Hum Mol Genet 4 (1995) 1183-1186
35. Zhou Y.Y., Lee L.Y., Ng S.Y., et al. UGT1A1 haplotype mutation among Asians in Singapore. Neonatology 96 (2009) 150-155
36. Pasanen M., Neuvonen P.J., and Niemi M. Global analysis of genetic variation in SLCO1B1. Pharmacogenomics 9 (2008) 19-33
37. Prachukthum S., Nunnarumit P., Pienvichit P., et al. Genetic polymorphisms in Thai neonates with hyperbilirubinemia. Acta Paediatr 98 (2009) 1106-1110
38. Chou S.C., Palmer R.H., Ezhuthachan S., et al. Management of hyperbilirubinemia in newborns: measuring performance by using a benchmarking model. Pediatrics 112 (2003) 1264-1273
39. Newman T.B., Kuzniewicz, Liljestrand P., Wi S., McCulloch C., and Escobar G.J. Numbers needed to treat with phototherapy according to American Academy of Pediatrics guidelines. Pediatrics 123 (2009) 1352-1359
40. Beutler E., Gelbert T., and Demina A. 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 (1998) 8170-8174
41. Maisels M.J., Gifford K., Antle C.E., et al. Jaundice in the healthy newborn infant: a new approach to an old problem. Pediatrics 81 (1988) 505-511
42. Sieg A., Arab L., Schlierf G., et al. Prevalence of Gilbert's syndrome in Germany. Dtsch Med Wochenschr 112 (1987) 1206-1208
43. Diamond L.K., Vaughn V.C., and Allen Jr. F.H. Erythroblastosis fetalis III. Prognosis in relation to clinical and serologic manifestations at birth. Pediatrics 6 (1950) 630-637
44. Armitage P., and Mollison P.L. Further analysis of controlled trials of treatment of haemolytic disease of the newborn. J Obstet Gynaecol Br Emp 60 (1953) 605-620
45. Walker W., and Mollison P.L. Haemolytic disease of the newborn: deaths in England and Wales during 1953 and 1955. Lancet 1 (1957) 1309-1314
46. Crosse V.M. The incidence of kernicterus (not due to haemolytic disease) among premature babies. In: Sass-Kortsak A. (Ed). Kernicterus (1961), University of Toronto Press, Toronto 4-9
47. Johnson L., Garcia M.L., Figueroa E., et al. Kernicterus in rats lacking glucuronyl transferase. Am J Dis Child 101 (1961) 322-349
48. Cannon C., Daood M.J., and Watchko J.F. Sex specific regional brain bilirubin content in hyperbilirubinemic Gunn rat pups. Biol Neonate 90 (2006) 40-45
49. Becu-Villabos D., Gonzalez Iglesias A., Diaz-Torga G., et al. Brain sexual differentiation and gonadotropins secretion in the rat. Cell Mol Neurobiol 17 (1997) 699-715
50. Clarke D.J., Moghrabi N., Monaghan G., et al. Genetic defects of the UDP-glucuronosyltransferase-1 (UGT1) gene that cause familial non-haemolytic unconjugated hyperbilirubinemias. Clin Chim Acta 266 (1997) 63-74
51. Perera M.A., Innocenti F., and Ratain M.J. Pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 polymorphisms. Are we there yet?. Pharmacotherapy 28 (2008) 755-768
52. Kawade N., and Onishi S. The prenatal and postnatal development of UDP glucuronyltransferase activity towards bilirubin and the effect of premature birth on this activity in human liver. Biochem J 196 (1981) 257-260
53. Coughtrie M.W., Burchell B., et al. The inadequacy of perinatal glucuronidation: immunoblot analysis of the developmental expression of individual UDP-glucuronosyltransferase isoenzymes in rat and human liver microsomes. Mol Pharmacol 34 (1988) 729-735
54. Sugatani J., Mizushima K., Osabe M., et al. Transcriptional regulation of human UGT1A1 gene expression through distal and proximal promoter motifs: implication of defects in the UGT1A1 promoter. Naunyn-Schmiedebergs Arch Pharmacol 377 (2008) 597-605
55. Valaes T. Bilirubin metabolism: review and discussion of inborn errors. Clin Perinatol 3 (1976) 177-209
56. Crigler Jr. J.F., and Najjar V.A. Congenital familial nonhemolytic jaundice with kernicterus. Pediatrics 10 (1952) 169-180
57. Gilbert A., and Lereboullet P. La cholemia simple familiale. Semaine Med 21 (1901) 241-243
58. Bosma P.J., Roy Chowdhury J., 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 (1995) 1171-1175
59. Powell L.W., Hemingway E., Billing B.H., et al. Idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome): a study of 42 families. N Engl J Med 277 (1967) 1108-1112
60. Innocenti F., Undevia S.D., Iyer L., et al. Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 22 (2004) 1382-1388
61. Odell G.B. Neonatal hyperbilirubinemia (1980), Grune & Stratton, New York
62. Oski F.A. Unconjugated hyperbilirubinemia. In: Avery M.E., and Taeusch H.W. (Eds). Diseases of the newborn (1984), WB Saunders, Philadelphia 630-632
63. Bancroft J.D., Kreamer B., and Gourley G.R. Gilbert syndrome accelerates development of neonatal jaundice. J Pediatr 132 (1998) 656-660
64. Roy-Chowdury N., Deocharan B., Bejjanki H.R., et al. Presence of the genetic marker for Gilbert syndrome is associated with increased level and duration of neonatal jaundice. Acta Paediatr 91 (2002) 100-102
65. Agrawal S.K., Kumar P., Rathi R., et al. UGT1A1 gene polymorphisms in North Indian neonates presenting with unconjugated hyperbilirubinemia. Pediatr Res 65 (2009) 675-680
66. Galanello R., Cipollina M.D., Carboni G., et al. Hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency and Gilbert's syndrome. Eur J Pediatr 158 (1999) 914-916
67. Ulgenalp A., Duman N., Schaefer F.V., et al. Analyses of polymorphism for UGT1*1 exon 1 promoter in neonates with pathologic and prolonged jaundice. Biol Neonate 83 (2003) 258-262
68. Iolascon A., Faienza M.F., Moretti A., and Perrotta S. Miraglia del Giudice E. UGT1 promoter polymorphism accounts for increased neonatal appearance of hereditary pherocyctosis. Blood 91 (1998) 1093
69. Maruo Y., Nishizawa K., Sato H., et al. Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate- glucuronosyltransferase gene. Pediatrics 106 (2000) e59
70. Monaghan G., McLellan A., McGeehan A., et al. Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn. J Pediatr 134 (1999) 441-446
71. Akaba K., Kimura T., Sasaki A., et al. Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese. Biochem Mol Biol Int 46 (1998) 21-26
72. Boo N.Y., Wong F.L., Wang M.K., and Othman A. Homozygous variant of UGT1A1 gene mutation and severe neonatal hyperbilirubinemia. Pediatr Int 51 (2009) 488-493
73. 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 (2002) 492-497
74. Lin Z., Fontaine J., and Watchko J.F. Coexpression of gene polymorphisms involved in bilirubin production and metabolism. Pediatrics 122 (2008) el56-el62
75. Maruo Y., Addario C.D., Mori A., et al. Two linked polymorphic mutations (A(TA)7TAA and T-3279G) of UGT1A1 as principal cause of Gilbert syndrome. Hum Genet 115 (2004) 525-526
76. Jirsa M., Petrasek J., and Vitek L. Linkage between A(TA)7TAA and -3279T → G mutations in UGT1A1 is not essential for pathogenesis of Gilbert syndrome. Liver Int 26 (2006) 1302-1303
77. Costa E., Vieira E., and dos Santos R. The polymorphism c.-3279T → G in the phenobarbital responsive enhancer module of the bilirubin UDP-glucuronosyltransferase gene is associated with Gilbert syndrome. Clin Chem 51 (2005) 2204-2206
78. Sai K., Saeki M., Saito Y., et al. UGT1A1 haplotypes associated with reduced glucuronidation and increased serum bilirubin in irinotecan-administered Japanese patients with cancer. Clin Pharmacol Ther 75 (2004) 501-515
79. Muraca M., Fevery J., and Blanckaert N. Relationships between serum bilirubins and production and conjugation of bilirubin. Studies in Gilbert's syndrome, Crigler-Najjar disease, hemolytic disorders and rat models. Gastroenterology 92 (1987) 309-317
80. Spivak W., DiVenuto D., and Yuey W. Non-enzymatic hydrolysis of bilirubin mono- and diglucuronide to unconjugated bilirubin in model and native bilirubin systems. Biochem J 242 (1987) 323-329
81. Maisels M.J., and Newman T.B. Kernicterus in otherwise healthy, breast-fed term newborns. Pediatrics 96 (1995) 730-733
82. Valaes T. Severe neonatal jaundice associated with glucose-6-phosphate dehydrogenase deficiency: pathogenesis and global epidemiology. Acta Paediatr Suppl 394 (1994) 58-76
83. Kaplan M., and Hammerman C. Glucose-6-phosphate dehydrogenase deficiency: a hidden risk for kernicterus. Semin Perinatol 28 (2004) 356-364
84. Beutler E. Glucose-6-phosphate dehydrogenase deficiency: a historical perspective. Blood 111 (2008) 16-24
85. Lin Z., Fontaine J.M., Freer D.E., et al. Alternative DNA-based newborn screening for glucose-6-phosphate dehydrogenase deficiency. Mol Genet Metab 86 (2005) 212-219
86. Cui Y., Konig J., Leier I., et al. Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6. J Biol Chem 276 (2001) 9626-9630
87. Daood M.J., and Watchko J.F. Ontogeny of human and murine solute carrier organic anion transporter 1B1 (SLCO1B1) expression in liver. EPAS 59 (2006) 5575 484
88. Lin R., Wang X., Wang Y., et al. Association of polymorphisms in four bilirubin metabolism genes with serum bilirubin in three Asian polulations. Hum Mutat 30 (2009) 609-615
89. Exner M., Minar E., Wagner O., and Schillinger M. The role of heme oxygenase-1 promoter polymorphisms in human disease. Free Radic Biol Med 37 (2004) 1097-1104
90. Endler G., Exner M., Schillinger M., et al. A microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with increased bilirubin and HDL levels but not with coronary artery disease. Thromb Haemost 91 (2004) 155-161
91. Yamda N., Yamaya M., Okinaga S., et al. Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema. Am J Hum Genet 66 (2000) 187-195
92. Kanai M., Akaba K., Sasaki A., et al. Neonatal hyperbilirubinemia in Japanese neonates: analysis of the heme oxygenase-1 gene and fetal hemoglobin composition in cord blood. Pediatr Res 54 (2003) 165-171
93. Immenschuh S., Shan Y., Kroll H., et al. Marked hyperbilirubinemia associated with the heme oxygenase-1 gene promoter microsatellite polymorphism in a boy with autoimmune hemolytic anemia. Pediatrics 119 (2007) e764-e767
94. Kadakol A., Sappal B.S., Ghosh S.S., et al. Interaction of coding region mutations and the Gilbert-type promoter abnormality of the UGT1A1 gene causes moderate degrees of unconjugated hyperbilirubinemia and may lead to neonatal kernicterus. J Med Genet 38 (2001) 244-249
95. Vockley J., Rinaldo P., Bennett M.J., Matern D., and Vladutiu G.D. Synergistic heterozygosity: disease resulting from multiple partial defects in one or more metabolic pathways. Mol Genet Metab 71 (2000) 10-18
96. Zangen S., Kidron D., Gelbart T., Roy-Chowdury N., Wang X., and Kaplan M. Fatal kernicterus in a girl deficient in glucose-6-phosphate dehydrogenase: a paradigm of synergistic heterozygosity. J Pediatr 154 (2009) 616-619
97. Lin J.P., Cupples L.A., Wilson P.W., Heard-Costa N., and O'Donnell C.J. Evidence for a gene influencing serum bilirubin on chromosome 2q telomere: a genomewide scan in the Framingham study. Am J Hum Genet 72 (2003) 1029-1034
98. Hunt S.C., Wu L.L., Hopkins P.N., and Williams R.R. Evidence for a major gene elevating serum bilirubin concentration in Utah pedigree. Arterioscler Thromb Vasc Biol 16 (1996) 912-917
99. Ki C.S., Lee K.A., Lee S.Y., et al. Haplotype structure of the UDP-glucuronosyltransferase A1A (UGT1A1) gene and its relationship to serum total bilirubin concentration in a male Korean population. Clin Chem 49 (2003) 2078-2081
100. Guillemette C., Levesque E., Harvey M., Bellemare J., and Menard V. UGT genomic diversity: beyond gene duplication. Drug Metab Rev (2009 Sep 30) (Epub ahead of print)
101. Gagnon J.F., Bernard O., Villeneuve L., Tetu B., and Guillemette C. Irinotecan inactivation is modulated by epigenetic silencing of UGT1A1 in colon cancer. Clin Cancer Res 12 (2006) 1850-1858
102. 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 (1993) 1239-1244
103. Sutomo R., Laosombat V., Sadewa A.H., et al. Novel missense mutation of the UGT1A1 gene in Thai siblings with Gilbert's syndrome. Pediatr Int 44 (2002) 427-432
104. 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 (2006) 91-97
105. 7 TAA allele in India and its interaction with a novel CAT insertion in promoter of the gene from bilirubin UDP-glucuronosyltransferase 1 gene. World J Gastroenterol 12 (2006) 2269-2275
106. Strassburg C.P., Kalthoff S., and Ehmer U. Variability and function of family 1 uridine-5'-diphosphate glucuronosyltransferases (UGT1A). Crit Rev Clin Lab Sci 45 (2008) 485-530
107. Hall D., Ybazeta G., Destro-Bisol G., Petzl-Erler M.L., and Di Rienzo A. Variability at the uridine diphosphate glucuronosyltransferase 1A1 promoter in human populations and primates. Pharmacogenetics 9 (1999) 591-599
108. Haverfield E.V., McKenzie C.A., Forrester T., et al. UGT1A1 variation and gallstone formation in sickle cell disease. Blood 105 (2005) 968-972
109. Han J.Y., Lim H.S., Shin E.S., et al. Comprehensive analysis of UGT1A1 polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin. J Clin Oncol 24 (2006) 2237-2244
110. Saito Y., Maekawa K., Ozawa S., and Sawada J. Genetic polymorphisms and haplotypes of major drug metabolizing enzymes in East Asians and their comparison with other ethnic populations. Curr Pharmacogenomics 5 (2007) 49-78