title: The role of UGT1A1 promoter polymorphism and exon-1 mutations in neonatal jaundice.
abstract: OBJECTIVE
  In the present study, we investigated the effects of promoter polymorphism and an exon-1 mutation (G71R) in the UGT1A1 gene in neonates with unexplained hyperbilirubinemia and direct Coombs-negative [DC(-)] ABO incompatibility.
  
  
  METHODS
  Two-hundred term neonates in their first week of life and without additional icterogenic factors were included in the study. Neonates with a serum total bilirubin (STB) level ≥17 mg/dL constituted the hyperbilirubinemia group (n = 100), while the control group comprised healthy neonates with a STB level <12.9 mg/dL (n = 100). The cases were further subdivided into unexplained hyperbilirubinemia (n = 50), ABO(+) hyperbilirubinemia (n = 50), ABO(-) control (n = 50), and ABO(+) control (n = 50) groups on the basis of the presence or absence of DC(-) ABO incompatibility. DNA was isolated from peripheral blood and amplified by PCR, and UGT1A1 gene promoter and exon-1 were sequenced to verify sequence alterations.
  
  
  RESULTS
  The frequency of TA6/6, TA6/7, TA7/7, and GGA/GGA, GGA/AGA, AGA/AGA genotypes was found to be 63.5%, 21%, 15.5%, and 91.5%, 8%, 0.5%, respectively. While both heterozygous and homozygous TA7 polymorphism increased risk of hyperbilirubinemia in the ABO(+) hyperbilirubinemia group (heterozygous OR 16.76, 95% CI:3.52-79.70, p < 0.0001; homozygous OR 6.81, 95% CI:1.98-23:42, p = 0.002), only heterozygous TA7 polymorphism increased jaundice risk (OR 5.08 95% CI:76-14.65, p = 0.003) in unexplained hyperbilirubinemia. But, the coexistence of G71R mutation and promoter polymorphism or G71R mutation and DC(-) ABO incompatibility did not increase the severity of hyperbilirubinemia (p > 0.05).
  
  
  CONCLUSIONS
  UGT1A1 gene promoter polymorphism and G71R mutation are possible risk factors for Turkish neonates with DC(-) ABO incompatibility and unexplained hyperbilirubinemia.
authors.affiliation: a Department of Pediatrics, Faculty of Medicine , Pamukkale University , Denizli , Turkey.
authors.forename: Hülya
authors.initials: H
authors.lastname: Halis
authors.affiliation: b Department of Pediatrics, Division of Neonatology, Faculty of Medicine , Pamukkale University , Denizli , Turkey.
authors.forename: Hacer
authors.initials: H
authors.lastname: Ergin
authors.affiliation: c Department of Biophysics, Faculty of Medicine , Pamukkale University , Denizli , Turkey.
authors.forename: Aylin
authors.initials: A
authors.lastname: Köseler
authors.affiliation: c Department of Biophysics, Faculty of Medicine , Pamukkale University , Denizli , Turkey.
authors.forename: Erol Ömer
authors.initials: EÖ
authors.lastname: Atalay
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology; D001787:Blood Group Incompatibility / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000235:genetics; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000235:genetics*; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D014421:Turkey; D000099148:UGT1A1 Enzyme
chemical_list: D000017:ABO Blood-Group System; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme
keywords: Hyperbilirubinemia; exon-1 mutation; promoter polymorphism