title: Association of HMOX1 gene promoter polymorphisms with hyperbilirubinemia in the early neonatal period.
abstract: BACKGROUND
  Heme oxygenase (HO) is the rate-limiting enzyme in the heme degradation pathway that produces bilirubin. The promoter region of human heme oxygenase-1 (HMOX1) contains a polymorphic (GT)n repeat that can regulate gene expression. Here, we investigated the association of (GT)n repeat length in the HMOX1 promoter region with neonatal hyperbilirubinemia in a population of Japanese term neonates.
  
  
  METHODS
  Using polymerase chain reaction and fragment analysis, we determined the number of (GT)n repeats in 149 Japanese neonates. To omit the effects of the G71R mutation in uridine diphosphoglucuronosyltransferase on hyperbilirubinemia, we excluded 41 neonates with the G71R mutation. As a result, 25 neonates with hyperbilirubinemia and 83 non-hyperbilirubinemic controls were included in this prospective case-control study. Allele and genotype frequencies of (GT)n repeats in the HMOX1 gene were compared between hyperbilirubinemic and non-hyperbilirubinemic control neonates.
  
  
  RESULTS
  The prevalence of short alleles (< 22 (GT)n repeats) was significantly higher in hyperbilirubinemic than in control neonates (18% vs 7%, P = 0.015). Hyperbilirubinemia was more frequent in homozygous or heterozygous short allele carriers than control neonates (28% vs 11%, respectively, P = 0.03). Possession of short alleles was significantly associated with the development of neonatal hyperbilirubinemia (OR, 3.1; 95%CI: 1.03-9.53).
  
  
  CONCLUSIONS
  Infants carrying short alleles (< 22 (GT)n repeats) in the HMOX1 gene promoter region appear to be at a higher risk for developing neonatal hyperbilirubinemia.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.|Department of Pediatrics, Takatsuki General Hospital, Takatsuki, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Katayama
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokota
authors.affiliation: Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wong
authors.affiliation: Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Stevenson
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Taniguchi-Ikeda
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Morioka
mesh_terms: D000483:Alleles; D001663:Bilirubin / Q000097:blood; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D004247:DNA; D051547:Heme Oxygenase-1; D001663:Bilirubin
keywords: genetic polymorphism; heme oxygenase-1; neonatal hyperbilirubinemia