title: Heme oxygenase-1 promoter polymorphisms and neonatal jaundice.
abstract: BACKGROUND
  Heme oxygenase (HO) is the initial, rate-limiting enzyme in the conversion of heme to bilirubin. Dinucleotide (GT)n repeat length in the promoter region of the encoding gene modulates transcription: shorter alleles, in contrast with longer allele counterparts, are associated with greater gene expression and should result in increased heme catabolism.
  
  
  OBJECTIVE
  We compared the rates of heme catabolism and plasma total bilirubin (TB) between HO-1 promoter genotypes of varying (GT)n repeat lengths in glucose-6-phosphate dehydrogenase (G6PD)-normal and -deficient neonates.
  
  
  METHODS
  HO-1 promoter length was determined from genomic DNA from previous studies by size discrimination of fluorescently-labeled PCR products with capillary electrophoresis. Sizing was confirmed by sequencing homozygote samples. Alleles were categorized as: short (≤24 GT repeats), medium (25-33 GT repeats), and long (≥34 GT repeats). Previously determined values for blood carboxyhemoglobin, corrected for inspired carbon monoxide (COHbc), and TB were used to determine the rate of heme catabolism and 3rd day TB values for each HO-1 promoter length genotype, respectively. G6PD Mediterranean was determined by PCR analysis.
  
  
  RESULTS
  Neither COHbc nor TB values were significantly different between various HO-1 promoter genotypes for either G6PD-normal or -deficient neonates.
  
  
  CONCLUSIONS
  In the steady state, HO-1 promoter genotypes, based on the length of (GT)n repeats, do not modulate heme catabolism or 3rd day TB values in either G6PD-normal or -deficient neonates.
authors.affiliation: Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Kaplan
authors.forename: Paul
authors.initials: P
authors.lastname: Renbaum
authors.forename: Cathy
authors.initials: C
authors.lastname: Hammerman
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Vreman
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wong
authors.forename: David K
authors.initials: DK
authors.lastname: Stevenson
mesh_terms: D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002263:Carboxyhemoglobin / Q000378:metabolism; D016022:Case-Control Studies; D016208:Databases, Factual; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006461:Hemolysis; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D015415:Biomarkers; D002263:Carboxyhemoglobin; D014453:Glucuronosyltransferase; D006418:Heme; D051547:Heme Oxygenase-1; D000099148:UGT1A1 Enzyme; C496541:HMOX1 protein, human