title: (TA)n UGT 1A1 promoter polymorphism: a crucial factor in the pathophysiology of jaundice in G-6-PD deficient neonates.
abstract: Increased heme catabolism has been reported in glucose-6-phosphate dehydrogenase (G-6-PD)-normal neonates who were also homozygous for (TA)7/(TA)7 (UGT1A1*28) uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT) promoter polymorphism (Gilbert syndrome). As G-6-PD deficiency is associated with increased hemolysis, we hypothesized that in G-6-PD-deficient neonates who also have the (TA)7/(TA)7 UGT promoter genotype, steady-state hemolysis would be even further increased. Male G-6-PD-deficient neonates were sampled for plasma total bilirubin (PTB), blood carboxyhemoglobin corrected for inhaled carbon monoxide in ambient air (COHbc) (an index of heme catabolism), and UGT (TA)n promoter genotype determination and compared with previously published G-6-PD-normal neonates. Although COHbc values were higher in the G-6-PD-deficient than in the G-6-PD-normal cohorts (0.97 +/- 0.32% of total Hb (tHb) versus 0.76 +/- 0.19% of tHb, p < 0.001), PTB values were similar (9.2 +/- 3.4 mg/dL versus 8.9 +/- 3.0 mg/dL, respectively, p = 0.3). Within the G-6-PD-deficient group, although COHbc values were alike between the three UGT promoter genotypes, PTB was higher in the (TA)7/(TA)7 homozygotes (11.1 +/- 4.0 mg/dL) compared with (TA)6/(TA)7 heterozygotes (9.1 +/- 3.2 mg/dL, p = 0.03) and wild-type (TA)6/(TA)6 homozygotes (8.8 +/- 3.4 mg/dL, p = 0.02). In the steady state, similar rates of hemolysis, but increased PTB in the G-6-PD- deficient, (TA)7/(TA)7 homozygotes, imply that (TA)7/(TA)7, homozygosity is central to increased PTB.
authors.affiliation: Department of Neonatology, Shaare Zedek Medical Center, Jerusalem 91031, Israel. kaplan@cc.huji.ac.il
authors.forename: Michael
authors.initials: M
authors.lastname: Kaplan
authors.forename: Paul
authors.initials: P
authors.lastname: Renbaum
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Vreman
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wong
authors.forename: Ephrat
authors.initials: E
authors.lastname: Levy-Lahad
authors.forename: Cathy
authors.initials: C
authors.lastname: Hammerman
authors.forename: David K
authors.initials: DK
authors.lastname: Stevenson
mesh_terms: D001663:Bilirubin / Q000097:blood; D002263:Carboxyhemoglobin / Q000032:analysis; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000235:genetics*; D007231:Infant, Newborn; D007565:Jaundice / Q000209:etiology*; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D002263:Carboxyhemoglobin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme