Differing pathogenesis of perinatal bilirubinemia in glucose-6-phosphate dehydrogenase-deficient versus-normal neonates.
The objective was to compare the contribution to perinatal bilirubinemia of hemolysis and UDP-glucuronosyltransferase (UGT) gene promoter polymorphism, seen in Gilbert's syndrome, between glucose-6-phosphate dehydrogenase (G-6-PD)-deficient and -normal neonates. Serum total bilirubin (STB) values from 52 G-6-PD-deficient and 166 G-6-PD-normal term, male neonates, sampled within 3 h of delivery (first sample) and on d 3 (second sample), were analyzed in relation to blood carboxyhemoglobin corrected for inspired CO (COHbc), an accurate index of hemolysis, and UGT promoter genotype. COHbc values (% total Hb) were greater in G-6-PD-deficient neonates than controls: first sample 1.00 +/- 0.25% versus 0.84 +/- 0.24%, p < 0.0001; second sample 0.83 +/- 0.20% versus 0.76 +/- 0.19%, p = 0.002. First sample COHbc and STB values did not correlate in either the G-6-PD-deficient or control groups, whereas second sample COHbc values correlated significantly with corresponding STB values in the control population only (r = 0.28, p = 0.0007). At second sampling, there was a higher allele frequency of the variant UGT promoter among those with STB values > or =75th percentile than those <75th among the G-6-PD-deficient neonates (0.60 versus 0.33, respectively, p = 0.025), but not controls (0.31 versus 0.40, respectively, p = 0.24). Among those infants with at least one variant UGT promoter allele, STB values were higher in the G-6-PD-deficient neonates than controls at second sampling only (181 +/- 56 microM versus 149 +/- 46 microM, respectively, p = 0.03). Both within and between the G-6-PD-deficient and control groups, our data demonstrate changing and differing contributions of hemolysis and UGT promoter polymorphism to bilirubinemia during the first 3 d of life.
Kaplan
M
M
Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel. kaplan@cc.huji.ac.il
Hammerman
C
C
Renbaum
P
P
Levy-Lahad
E
E
Vreman
H J
HJ
Stevenson
D K
DK
D001483:Base Sequence; D015331:Cohort Studies; D017931:DNA Primers; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D006932:Hyperbilirubinemia / Q000201:enzymology / Q000209:etiology*; D007231:Infant, Newborn; D008297:Male; D016297:Mutagenesis, Site-Directed; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D017931:DNA Primers; D005954:Glucosephosphate Dehydrogenase; D014453:Glucuronosyltransferase