The role of UGT1A1 promoter polymorphism and exon-1 mutations in neonatal jaundice.

ABSTRACT

OBJECTIVE: In the present study, we investigated the effects of promoter polymorphism and an exon-1 mutation (G71R) in the UGT1A1 gene in neonates with unexplained hyperbilirubinemia and direct Coombs-negative [DC(-)] ABO incompatibility. METHODS: Two-hundred term neonates in their first week of life and without additional icterogenic factors were included in the study. Neonates with a serum total bilirubin (STB) level ≥17 mg/dL constituted the hyperbilirubinemia group (n = 100), while the control group comprised healthy neonates with a STB level <12.9 mg/dL (n = 100). The cases were further subdivided into unexplained hyperbilirubinemia (n = 50), ABO(+) hyperbilirubinemia (n = 50), ABO(-) control (n = 50), and ABO(+) control (n = 50) groups on the basis of the presence or absence of DC(-) ABO incompatibility. DNA was isolated from peripheral blood and amplified by PCR, and UGT1A1 gene promoter and exon-1 were sequenced to verify sequence alterations. RESULTS: The frequency of TA6/6, TA6/7, TA7/7, and GGA/GGA, GGA/AGA, AGA/AGA genotypes was found to be 63.5%, 21%, 15.5%, and 91.5%, 8%, 0.5%, respectively. While both heterozygous and homozygous TA7 polymorphism increased risk of hyperbilirubinemia in the ABO(+) hyperbilirubinemia group (heterozygous OR 16.76, 95% CI3.52-79.70, p < 0.0001; homozygous OR 6.81, 95% CI1.98-2342, p = 0.002), only heterozygous TA7 polymorphism increased jaundice risk (OR 5.08 95% CI76-14.65, p = 0.003) in unexplained hyperbilirubinemia. But, the coexistence of G71R mutation and promoter polymorphism or G71R mutation and DC(-) ABO incompatibility did not increase the severity of hyperbilirubinemia (p > 0.05). CONCLUSIONS: UGT1A1 gene promoter polymorphism and G71R mutation are possible risk factors for Turkish neonates with DC(-) ABO incompatibility and unexplained hyperbilirubinemia.