Glucose-6-phosphate dehydrogenase deficiency, the UDP-glucuronosyl transferase 1A1 gene, and neonatal hyperbilirubinemia.
OBJECTIVE
Coinheritance of the A(TA)7TAA promoter variant in the uridine 5'-diphosphate-glucuronosyl transferase 1A1 (UGT1A1) gene and glucose-6-phosphate dehydrogenase (G6PD) deficiency is crucial to hyperbilirubinemia in white male neonates. A variation rate of 29.3% was determined within the coding region of the UGT1A1 gene in Taiwanese subjects, suggesting the hypothesis that this variation may influence incidence of hyperbilirubinemia in male neonates with G6PD deficiency.


METHODS
The full sequence of the UGT1A1 gene was identified for 212 G6PD-deficient and 232 control male neonates by using polymerase chain reaction (PCR).


RESULTS
Both study and control groups were divided into 5 subgroups according to their UGT1A1 genotypes. Most subjects carried G to A variation at nucleotide 211 for both genotypes of heterozygous variation within coding region and homozygous variation. No significant differences were noted for the frequencies of the 5 UGT1A1 genotypes, gestation age, and birth weight comparing the G6PD-deficient and control groups. The incidence of hyperbilirubinemia, however, was significantly higher for the study group than for the controls. This difference was noted only for the subgroup bearing the homozygous variant of the UGT1A1 gene. In the subgroup of homozygous variation, the serum bilirubin value was significantly higher for G6PD-deficient neonates than for controls. All 11 G6PD-deficient neonates with the homozygous 211 G to A variation suffered from hyperbilirubinemia.


CONCLUSIONS
The results indicate that carriage of the homozygous 211 G to A variation within the coding region in the UGT1A1 gene is an additive risk factor for neonatal hyperbilirubinemia in G6PD-deficient Taiwanese male neonates.
Huang
Ching-Shan
CS
Department of Laboratory Medicine, Cathay General Hospital, Taipei, Taiwan. pcsh@ms1.cgh.org
Chang
Pi-Feng
PF
Huang
May-Jen
MJ
Chen
En-Sung
ES
Chen
Wu-Charng
WC
D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics*; D009154:Mutation; D012016:Reference Values; D000099148:UGT1A1 Enzyme
D005954:Glucosephosphate Dehydrogenase; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme