The role of UGT1A1 promoter polymorphism and exon-1 mutations in neonatal jaundice. (17th November 2017)

• Record Type: Journal Article
• Authors: Halis, Hülya; Ergin, Hacer; Köseler, Aylin; Atalay, Erol Ömer
• Is Part Of: Journal of maternal-fetal & neonatal medicine. Volume 30:Number 22(2017)
• Page Start: 2658
• Page End: 2664
• Publication Date: 2017-11-17
• Subjects: Hyperbilirubinemia -- promoter polymorphism -- exon-1 mutation; Obstetrics -- Periodicals; Perinatology -- Periodicals; Infants (Newborn) -- Diseases -- Periodicals; Neonatology -- Periodicals; 618.2
• DOI: 10.1080/14767058.2016.1261105
• Languages: English
• ISSNs: 1476-7058

Abstract

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.