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% CI:3.52-79.70, p < 0.0001; homozygous OR 6.81, 95% CI:1.98-23:42, p = 0.002), only heterozygous TA7 polymorphism increased jaundice risk (OR 5.08 95% CI:76-14.65, 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.

Keywords:

• Hyperbilirubinemia
• promoter polymorphism
• exon-1 mutation

Disclosure statement

The other authors have indicated they have no potential conflicts of interest to disclose.

Additional information

Funding

This study was supported by the Pamukkale University’s scientific research projects unit (project no: TPF021).