UGT1A1 Gene Polymorphisms in North Indian Neonates Presenting with Unconjugated Hyperbilirubinemia

Genetic factors are implicated in pathogenesis of neonatal hyperbilirubinemia. In this nested case-control Study, we determined 1) frequency of thymine-adenine (TA)(n) promoter polymorphism and Gly71Arg mutation in uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene in neonates >= 35-wk gestation presenting with bilirubin levels >= 18 mg/dL and controls, 2) interaction among (TA)(n) promoter polymorphism, glucose-6-phosphate dehydrogenase (G6PD) gene mutations, and peak bilirubin. The number of TA repeats was assessed by PCR-single-strand conformation polymorphism (SSCP) analysis and Gly71Arg mutation by PCR-RFLP. Fifty samples of both mutations were verified with DNA sequencing. One hundred twenty-seven neonates were enrolled (77 hyperbilirubinemics, 50 controls). The incidence of (TA)(n) polymorphism was higher in babies with hyperbilirubinemia 189.6% vs. 50%, OR 8.63 (95% CI, 3.2-24.1)]. Gly71Arg Mutation was not found either in hyperbilirubinemics or controls. A novel polymorphism (Ala72Pro) at codon position 72 of exon 1 was detected in all 50 samples (21 hyperbilirubinemics, 29 controls), which were sequenced. Presence of variant (TA)(n) promoter (adjusted OR, 10.6; 95% CI, 3.3-34.2), G6PD deficiency (adjusted OR, 20.6; 95% CI, 3.6-117.3), and history of jaundice in sibling requiring phototherapy (adjusted OR, 12.6; 95% CI, 1.1-141.6) were independent risk factors for bilirubin levels >= 18 mg/dL. (Pediatr Res 65: 675-680, 2009)