title: Molecular genetics of unconjugated hyperbilirubinemia in Taiwanese.
abstract: In bilirubin metabolism, increased destruction of erythrocytes, defect in the function of organic anion transporter polypeptide 2 (OATP2) or UDP-glucuronosyltransferase 1A1 (UGT1A1) may result in unconjugated hyperbilirubinemia. Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is known to be associated with the development of neonatal hyperbilirubinemia, it was observed that in neonates severe hyperbilirubinemia caused by G6PD deficiency, without associated polymorphisms in the UGT1A1 or the OATP2 gene, was preventable. Variations at the nucleotide (nt) 388 of OATP2 gene and nt-211 of UGT1A1 gene, were found to be a risk factor for severe hyperbilirubinemia amongst Taiwanese neonates, respectively. G6PD deficiency, variations at nts 388 and 521 of OATP2 gene, and variations at nt-211 and in the promoter area of UGT1A1 gene were reported to be the risk factors for the occurrence of mild hyperbilirubinemia amongst Taiwanese adults. The status of the haplotypes of G6PD, OATP2, and UGT1A1 genes affected the odds ratio and the bilirubin levels in the hyperbilirubinemic subjects. Moreover, carriage of the variant-211 UGT1A1 allele, as well as UGT1A7*3 allele, was demonstrated to represent a risk factor for the development of, and a determinant for, metastases associated with Taiwanese colorectal-cancer patients. Further investigation is warranted to evaluate this phenomenon.
authors.affiliation: Department of Medical Technology, Fooyin University, 151 Chin-Hsueh Rd., Ta-Liao Hsiang, Kaohsiung, Hsien, 831, Taiwan. chsh.huang@msa.hinet.net
authors.forename: Ching-Shan
authors.initials: CS
authors.lastname: Huang
mesh_terms: D000328:Adult; D001663:Bilirubin / Q000378:metabolism; D003414:Crigler-Najjar Syndrome / Q000235:genetics; D014644:Genetic Variation; D005878:Gilbert Disease / Q000235:genetics; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006932:Hyperbilirubinemia / Q000235:genetics*; D006933:Hyperbilirubinemia, Hereditary / Q000235:genetics / Q000378:metabolism; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D012307:Risk Factors; D013624:Taiwan; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D027381:Liver-Specific Organic Anion Transporter 1; D000099148:UGT1A1 Enzyme