Browse > Article

1828G>A polymorphism of the UDP-glucuronosyltransferase gene (UGT1A1) for neonatal hyperbilirubinemia in Koreans  

Kim, Ja Young (Department of Pediatrics, Sung-Ae General Hospital)
Kim, Mi Yeoun (Department of Pediatrics, Sung-Ae General Hospital)
Kim, Ji Sook (Department of Pediatrics, Sung-Ae General Hospital)
Kim, Eun Ryoung (Department of Pediatrics, Sung-Ae General Hospital)
Yoon, Seo Hyun (Department of Pharmacology, College of Medicine, Kyunghee University)
Lee, Hee Jae (Department of Pharmacology, College of Medicine, Kangwon National University)
Chung, Joo Ho (Department of Pharmacology, College of Medicine, Kyunghee University)
Publication Information
Clinical and Experimental Pediatrics / v.49, no.1, 2006 , pp. 34-39 More about this Journal
Abstract
Purpose : The incidence of neonatal hyperbilirubinemia is twice as high in East Asians as in Caucasians. However, its metabolic basis has not been clearly explained. The UDP-glucuronosyltransferase gene(UGT1A1) mutation was found to be a risk factor of neonatal hyperbilirubinemia. We studied whether neonatal hyperbilirubinemia is associated with the 1828G>A(rs 10929303) polymorphism of the UGT1A1 gene, which encodes for a key enzyme of bilirubin metabolism. Methods : The genomic DNA was isolated from 80 Korean full term neonates who had greater than a 12 mg/dL level of serum bilirubin with no obvious cause, and the genomic DNA was also isolated from 164 Korean neonates of the control population. We studied a single nucleotide polymorphism (SNP) of 1828G>A in the untranslated region of the UGT1A1 gene by direct sequencing. Results : Three of the 80 neonates with a serum bilirubin level above 12 mg/dL had homozygous mutations and 10 of the 80 neonates with a serum bilirubin level above 12 mg/dL had heterozygous mutations. Thirteen of the 164 neonates of the control group had homozygous mutations and 16 neonates of the control group had heterozygous mutations. The allele frequency of 1828G>A polymorphism of UGT1A1 in the hyperbilirubinemia group was 10.0 percent, which was not significantly different from the allele frequency of 12.8 percent in the control group. Conclusion : In this study, the 1828G>A polymorphism of the UGT1A1 gene was detected in the Korean neonates with neonatal hyperbilirubinemia. Our results indicated that this SNP is not associated with the prevalence of hyperbilirubinemia in Koreans.
Keywords
UDP-glucuronosyltransferase gene(UGT1A1); Neonatal hyperbilirubinemia; Polymorphism;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Maisels MJ. Jaundice. In : Avery GB, Fletcher MA, Mac- Donald MG, editors. Neonatology : pathophysiology and management of the newborn. 5th ed. Philadelphia : JB Lippincott Co, 1999:765-819
2 Brown WR, Boon WH. Ethic group differences in plasma bilirubin levels of full-term, healthy Singapore newborns. Pediatrics 1965;36:745-51
3 Newman TB, Easterlin MJ, Goldman ES, Stevenson DK. Laboratory evaluation of jaundice in newborns. Am J Dis Child 1990;144:364-8   DOI
4 Drew JH, Kitchen WH. Jaundice in infants of greek parentage : the unknown factor may be environmental. J Pediatr 1976;89:248-52   DOI
5 Hong KW, Kang H, Kim IS, Kim JS, Kim ER, Lee HJ, et al. Polymorphism of UDP-glucuronosyltransferase gene (UGT1A1) of neonatal hyperbilirubinemia in Korea. Korean J Pediatr 2004;47:18-23
6 Akaba K, Kimura T, Sasaki A, Tanabe S, Wakabayashi T, Hiroi M, et al. Neonatal hyperbilirubinemia and a common mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese. J Hum Genet 1999;44:22-5   DOI
7 Huang CS, Luo GA, Huang MJ, Yu SC, Yang SS. Variations of the bilirubin uridine-diphosphoglucuronosyl transferase 1A1 gene in healthy Taiwanese. Pharmacogenetics 2000;10:539-44   DOI
8 Kim YH, Yeon JE, Jung GM, Kim HJ, Kim JS, Byun KS, et al. A study of polymorphism in UDP-glucuronyltransferase 1(UGT-1A1) promoter gene in Korean patients with Gilbert's syndrome. Korean J Hepatol 2002;8:132-8
9 Linn S, Schoenbaum SC, Monson RR, Rosner B, Stubblefield PG, Ryan KJ. Epidemiology of neonatal hyperbilirubinemia. Pediatrics 1985;75:770-4
10 Huang CS, Chang PF, Huang MJ, Chen ES, Hung KL, Tsou KI. Relationship between bilirubin UDP-glucuronosyltransferase 1A1 gene and neonatal hyperbilirubinemia. Pediatr Res 2002;52:601-5   DOI
11 Kanai M, Kijima K, Shirahata E, Sasaki A, Akaba K, Umetsu K, et al. Neonatal hyperbilirubinemia and the bilirubin uridine diphosphate glucuronosyltransferase gene : the common -3263T> G mutation of phenobabital response enhancer module is not associated with the neoanatal hyperbilibinemia in Japanese. Pediatr Int 2005;47:137-41   DOI   ScienceOn
12 Huang CS, Chang PF, Huang MJ, Chen ES, Chen WC. Glucose-6-phosphate dehydrogenase deficiency, the UDPglucuronosyl transferase 1A1 gene, and neonatal hyperbilirubinemia. Gastroenterology 2002;123:127-33   DOI   ScienceOn
13 Bancroft JD, Kreamer B, Gourley GR. Gilbert,s syndrome accelerates development of neonatal jaundice. J Pediatr 1998;132:656-60   DOI   ScienceOn
14 Yamamoto K, Sato H, Fujiyama Y, Doida Y, Bamba T. Contribution of two missense mutations(G71R and Y486D) of the bilirubin UDP glucosyltransferase(UGT1A1) gene phenotypes of Gilbert's syndrome and Crigler-Najjar syndrome type II. Biochim Biophys Acta 1998;1406:267-73   DOI
15 Maruo Y, Addario CD, Mori A, Iwai M, Takahashi H, Sato H, et al. Two linked polymorphic mutations (A(TA)7TAA and T-3279G) of UGT1A1 as the principal cause of Gilbert syndrome. Hum Genet 2004;115:525-6   DOI   ScienceOn
16 Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronyltransferase 1 in Gilbert's syndrome. N Engl J Med 1995;333:1171-5   DOI   ScienceOn
17 Khoury MJ, Calle EE, Joesoef RM. Recurrence risk of neonatal hyperbilirubinemia in siblings. Am J Dis Child 1988; 142:1065-9
18 Nielsen HE, Haase P, Blaabjerg J, Stryhn H, Hilden J. Risk factors and sib correlation in physiological neonatal jaundice. Acta Paediatr Scand 1987;76:504-11   DOI
19 Ritter JK, Crawford JM, Owens IS. Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells. J Biol Chem 1991;266:1043-7
20 Burchell B, Hume R. Molecular genetic basis of Gilbert's syndrome. J Gastroenterol Hepatol 1999;14:960-6   DOI   ScienceOn
21 Huang MJ, Kug KE, Teng Hc, Tang KS, Weng HW, Hung CS. Risk factors for severe hyperbilirubinemia in neonates. Pediatr Res 2004;56:682-9   DOI   ScienceOn
22 Akaba K, Kimura T, Sasaki A, Tanabe S, Ikegami T, Hashimoto M, et al. Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate glucuronosyltransferase gene : A common missense mutation among Japanese, Koreans and Chinese. Biochem Molec Biol Int 1998; 46:21-6
23 Friedman L, Lewis PJ, Clifton P, Bulpitt CJ. Factors influencing the incidence of neonatal jaundice. Br Med J 1978;1: 1235-7   DOI
24 Beutler E, Gelbart T, Demina A. Racial variability in the UDP-glucuronosyl transferase 1(UGT1A1) promoter : A balanced polymorphism for regulation of bilirubin metabolism?Proc Natl Acad Sci USA 1998;95:8170-4
25 Yamamoto A, Nishio H, Waku S, Yokoyama N, Yonetani M, Uetani Y, et al. Gly71Arg mutation of the bilirubin UDP-glucuronosyltransferase 1A1 gene is associated with neonatal hyperbilirubinemia in the Japanese population. Kobe J Med Sci 2002;48:73-7.
26 Sutomo R, Talib NA, Yusoff NM, Van Rostenberghe H, Sadewa AH, Sunarti, et al. Screening for G71R mutation of the UGT1A1 gene in the Javanese- Indonesian and Malay- Malaysian populations. Pediatr Int 2004;46:565-9   DOI   ScienceOn
27 Horiguchi T, Bauer C. Ethnic differences in neonatal jaundice : Comparison of Japanese and Caucasian newborn infants. Am J Obstet Gynecol 1975;121:71-4   DOI
28 Koiwai O, Nishizawa M, Hasada K, Aono S, Adachi Y, Mamiya N, et al. Gilbert's syndrome is caused by a heterozygous missense mutation in the gene for bilirubin UDPglucuronosyltransferase. Hum Mol Genet 1995;4:1183-6.   DOI   ScienceOn
29 Kadakol A, Ghosh SS, Sappal BS, Sharma G, Chowdhury NR. Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase(UGT1A1) causing Crigler- Najjar and Gilbert syndromes : correlation of genotype to phenotype. Hum Mutat 2000;16:297-306   DOI   ScienceOn
30 Maruo Y, Nishizawa K, Sato H, Doida Y, Shimada M. Association of neonatal hyperbilirubinemia with bilirubin UDP-glucuronosyltransferase polymorphism. Pediatrics 1999; 103:1224-7   DOI   ScienceOn
31 Monaghan G, Ryan M, Seddon R, Hume R, Burchell B. Genetic variation in bilirubin UDP-glucuronosyltransferase gene promoter and Gilbert's syndrome. Lancet 1996;347: 578-81   DOI   ScienceOn
32 Gale R, Seidman DS, Dollberg S, Stervenson DK. Epidemiology of neonatal jaundice in the Jerusalem population. J Pediatr Gastroenterol Nutr 1990;10:82-6   DOI
33 Kang H, Lim JH, Kim JS, Kim ER, Kim SD, Lee HJ, et al. The association of neonatal hyperbilirubinemia with UGT1A1 and CYP1A2 gene polymorphism in Korean neonate.Korean J Pediatr 2005;48:35-41
34 Ando Y, Chida M, Nakayama K, Saka H, Kamataki T. The UGT1A1*28 allele is relatively rare in a Japanese population. Pharmacogenetics 1998;8:357-60   DOI
35 Raijmarkers MT, Jansen PL, Steegers EA, Peters WH. Association of human liver bilirubin UDP-glucuronyltransferase activity with a polymorphism in the promoter region of the UGT1A1 gene. J Hepatol 2000;33:348-51   DOI   ScienceOn
36 Takeuchi K, Kobayashi Y, Tamaki S, Maruo Y, Araki J, Mifuji R, et al. Genetic polymorphisms of bilirubin uridine diphosphate glucrononsyltransferase gene in Japanese patients with Crigler-Najjar syndrome or Gilbert's syndrome as well as in healthy Japanese subjects. J Gstroenterol Hepatol 2004;19:955-7   DOI   ScienceOn
37 Sugatani J, Yamakawa K, Yoshinari K, Machida T, Takagi H, Mori M, et al. Identification of a defect in the UGT1A1 gene promoter and its association with hyperbilirubinemia. Biochem Biophys Res Commun 2002;292:492-7   DOI   ScienceOn