Jaundiced glucose-6-phosphate dehydrogenase deficient (G-6-PD def) neonates have deficient bilirubin conjugation, with a serum bilirubin profile akin to that of Gilbert Syndrome (GS). A variant promotor, (long TATAA element with an extra TA), has been identified in the gene for bilirubin UDP glucuronosyl transferase 1 (UDPGT) in GS. Aim: To determine whether the presence of GS allele is a risk factor for neonatal jaundice (NJ), in G-6-PD deficient and normal populations. Methods: Term, male neonates, screened for G-6-PD def, were observed for NJ, defined as peak serum total bilirubin ≥15mg/dL. DNA extracted from umbilical cord blood was analyzed by PCR for UDPGT promotor polymorphism associated with GS. Using G-6-PD normal with no GS allele as baseline, odds ratio (OR) for developing NJ was determined by logistic regression analysis, with jaundice as dependent, and GS genotype and G-6-PD status as independent variables. Results: GS allele frequency was similar in the G-6-PD defs and normals (30% vs. 29%, NS). 12/51 (23.5%) of the G-6-PD defs developed NJ, vs. 9/116 (7.8%) of normals(p=0.01). Table shows OR for NJ: Correction for ABO incompatibility, birthweight or gestational age did not change OR.

Table 1
Full size table

Conclusions: GS allele presence was associated with increased probability of NJ in an allele dose dependent fashion, in both G-6-PD normal, but especially G-6-PD deficient neonates. The risk for NJ in G-6-PD normals homozygous for GS, contrasts with the risk in G-6-PD defs both hetero- and homozygous for GS. This suggests interaction between G-6-PD deficiency and GS allele in the pathogenesis of the associated NJ.