Impact of G-6-PD, SLCO1B1 and UGT1A1 variants on severity of neonatal hyperbilirubinemia in Northeastern Thailand

Abstract

Neonatal hyperbilirubinemia is a common complication in Thailand. The polymorphisms of SLCO1B1 (encoding solute carrier organic anion transporter 1B1) and UGT1A1 (uridine diphosphate glucuronosyltransferase 1A1) as well as G-6-PD mutations associated with glucose-6-phosphate dehydrogenase deficiency have been reported as genetic risk factors for this condition. This study investigated the association between these genetic variations with severity of neonatal hyperbilirubinemia in
northeastern Thai newborns. Neonates (n = 204) with hyperbilirubinemia were analyzed for common G-6-PD mutations and polymorphisms of SLCO1B1 c.388G>A, SLCO1B1 c.521T>C and UGT1A1 g.-3279T>G using
restriction fragment length polymorphism-PCR assay. G-6-PD mutations are significant genetic risk factors for severe neonatal hyperbilirubinemia indicated by significantly higher peak total serum bilirubin (coefficient = 0.93, 95% CI: 0.22-1.64, p-value = 0.011), longer duration of phototherapy (coefficient = 14.45, 95% CI: 6.92-21.99, p-value = 0.0001), early (≤48 hours) onset of hyperbilirubinemia (OR = 2.29, 95% CI: 1.22-4.31, p-value
= 0.010) and more hospital readmission (OR = 4.13, 95% CI: 1.09-15.67, p-value = 0.037). SLCO1B1 c.388G>A, SLCO1B1 c.521T>C and UGT1A1 g.-3279T>G polymorphisms were present in northeastern Thai neonates
with allele frequencies similar to those of other Asian populations, but they were not associated with severity of neonatal hyperbilirubinemia. These findings indicate that if genetic factors impacting on neonatal
hyperbilirubinemia are to be more fully understood, a larger cohort study of these genetic variations and other pertinent genes involved in neonatal bilirubin will be needed.