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Hemolysis and bilirubin conjugation in association with UDP‐glucuronosyltransferase 1A1 promoter polymorphism
Author(s) -
Kaplan Michael,
Hammerman Cathy,
Rubaltelli Firmino F.,
Vilei Maria T.,
LevyLahad Ephrat,
Renbaum Paul,
Vreman Hendrik J.,
Stevenson David K.,
Muraca Maurizio
Publication year - 2002
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2002.32526
Subject(s) - bilirubin , hemolysis , heme , medicine , glucuronosyltransferase , genotype , unconjugated hyperbilirubinemia , allele , chemistry , hemoglobin , gilbert's syndrome , endocrinology , pathogenesis , catabolism , promoter , microbiology and biotechnology , biology , gene , biochemistry , metabolism , enzyme , gene expression , microsome
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.