Hemolysis and bilirubin conjugation in association with UDP-glucuronosyltransferase 1A1 promoter polymorphism.
Hemolysis may contribute to hyperbilirubinemia in Gilbert's syndrome. The authors examined blood carboxyhemoglobin corrected for inspired CO (COHbc) to index heme catabolism and serum conjugated bilirubin fractions to reflect bilirubin conjugation. Both parameters were related to UDP-glucuronosyltransferase 1A1 (UGT) promoter polymorphism, associated with Gilbert's syndrome, in term male newborns. COHbc was expressed as percentage of total hemoglobin, and total conjugated bilirubin (TCB) value as a percentage of serum total bilirubin (STB), (TCB/STB[%]). A production/conjugation index, COHbc/(TCB/STB[%]), represented bilirubin production divided by conjugation. UGT promoter genotype was designated according to the number of promoter TA insertions in each allele: 6/6, homozygous normal; 6/7, heterozygous; 7/7, homozygous variant. STB and COHbc values were higher in the 7/7 subgroup than the other counterparts (P <.01). The COHbc/(TCB/STB[%]) was higher in the 7/7 than either the 6/6 or 6/7 subsets (1.93 [1.31-2.88] vs. 0.85 [0.51-1.72] and 0.84 [0.53-1.87], respectively; P <.01). In conclusion, 7/7 UGT promoter polymorphism was associated with increased blood COHbc values (unexpected finding) as well as diminished serum total conjugated bilirubin ratios (expected finding). The increased hemolysis may contribute to the pathogenesis of increased STB values seen in Gilbert's syndrome, and exacerbate neonatal hyperbilirubinemia associated with the promoter polymorphism.
Kaplan
Michael
M
Department of Neonatology, Clinical Genetics Service, Shaare Zedek Medical Center, Faculty of Medicine of the Hebrew University, Jerusalem, Israel. kaplan@cc.huji.ac.il
Hammerman
Cathy
C
Rubaltelli
Firmino F
FF
Vilei
Maria T
MT
Levy-Lahad
Ephrat
E
Renbaum
Paul
P
Vreman
Hendrik J
HJ
Stevenson
David K
DK
Muraca
Maurizio
M
D001663:Bilirubin / Q000097:blood*; D002263:Carboxyhemoglobin / Q000032:analysis; D015331:Cohort Studies; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006461:Hemolysis; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011110:Polymorphism, Genetic / Q000502:physiology*; D012016:Reference Values; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D002263:Carboxyhemoglobin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme