title: Effect of genetic variants of bilirubin metabolism on the degree of hyperbilirubinemia in African-American newborns.
abstract: The objective of our study was to measure the effect of genetic variants of these two enzymes, UGT1A1 and SLCO1B1, in the bilirubin metabolic pathway on the degree of hyperbilirubinemia in a cohort of African-American (AA) infants from our well-baby nursery. In addition, a second objective was to document the types and frequencies of genetic variations of these enzymes in our cohort.
  
  
  
  A prospective study of 180 AA infants from the Well Baby Nursery of an inner city community hospital, all of whose mothers were type O pos. Sixty infants were ABO-incompatible direct antiglobulin test (DAT) pos, 60 were ABO-incompatible DAT neg and 60 were type O+. Blood for carboxyhemoglobin (COHb) and variants of the enzymes uridine diphosphoglucuronosyltransferase 1A1 and hepatic solute carrier organic anion transporter 1B1 (SLCO1B1) was drawn at the time of the infants' initial bilirubin, and the infants' precise percentile on the Bhutani nomogram was calculated.
  
  
  
  Variants in the two enzymes studied were quite common. In total, 21.1% were positive for a Gilbert phenotype, whereas an additional 42.4% were heterozygous for the *28 or *37 variant of UGT1A1. In total, 67.2% were homozygous for the *60 variant of the phenobarbital responsive enhancer module. In total, 41.1% were homozygous for the *1b variant of SLCO1B1, whereas an additional 12.7% were positive for the *4 variant of this gene. In total, 20.6% of infants had variations in both genes. Using logistic regression when COHbc was assessed with each of the different variants, only COHbc (P<0.0001 to 0.0004) was significantly associated with the level of hyperbilirubinemia as defined by the Bhutani nomogram.
  
  
  
  Although we have found quite a large number of genetic variants of the UGT1A1 and SLCO1B1 genes in the AA population, it does not appear that they have a significant impact on the incidence of hyperbilirubinemia among this group of infants.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Einstein Medical Center, Philadelphia, PA, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Schutzman
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Baudhuin
authors.affiliation: Department of Pediatrics, Michigan State University, Lansing, MI, USA.
authors.forename: E
authors.initials: E
authors.lastname: Gatien
authors.affiliation: Division of Neonatology, Saint Christopher's Hospital for Children, Philadelphia, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ajayi
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Wong
mesh_terms: D001741:Black or African American / Q000235:genetics*; D001663:Bilirubin / Q000097:blood* / Q000378:metabolism*; D003298:Coombs Test; D005260:Female; D014644:Genetic Variation; D014453:Glucuronosyltransferase / Q000235:genetics; D006579:Heterozygote; D006650:Histocompatibility Testing; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D007231:Infant, Newborn; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics; D016015:Logistic Models; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D027381:Liver-Specific Organic Anion Transporter 1; D000099148:UGT1A1 Enzyme; C503999:SLCO1B1 protein, human