Genetic association of UGT1A1 promoter c.-3279T>G, and c.-3156G>A variants with neonatal hyperbilirubinemia in an Iranian Population

Background: Several studies have reported that two promotor c.-3279T>G, and c.-3156G>A variants in UDP- glucuronosyltransferase (UGT1A1) gene may contribute to neonatal hyperbilirubinemia. However, these variants have not been investigated in Iranian neonates. This cross-sectional study aimed to determine if the UGT1A1 promoter variants are significant risk factors associated with neonatal hyperbilirubinemia. Methods: A total of 178 unrelated neonates comprised 95 infants with neonatal jaundice and 83 healthy controls were enrolled. Using fresh blood DNA, each individual was genotyped by PCR-RFLP and COP-PCR at nucleotides -3279, and -3156, respectively. Logistic regression analyses were performed to assess the association of UGT1A1 promoter variants with the presence of significant hyperbilirubinemia. Anthropometric indices, and clinical variables were also compared between the different genotype groups. Results: Allele and genotype analysis of the c.-3279T>G, and c.-3156G>A variants showed no significant association with the risk of neonatal hyperbilirubinemia neither in the crude nor after adjustment for gestational age, gender, and birth weight in different genetic models (P>0.05). However, in haplotype-association analysis, only one haplotype (A-T) was found to be associated with the risk of neonatal hyperbilirubinemia (OR=0.19, 95% CI; [0.18–0.20], P=0.001). Conclusion: This study failed to demonstrate c.-3279T>G, and c.-3156G>A variants alone may contribute to the risk of neonatal hyperbilirubinemia in Iranian neonates. However, A-T haplotype may play a significant role in increasing the risk of hyperbilirubinemia.