Profiling of UGT1A1*6, UGT1A1*60, UGT1A1*93, and UGT1A1*28 Polymorphisms in Indonesian Neonates With Hyperbilirubinemia Using Multiplex PCR Sequencing

Abstract

<b>Background:</b> Single nucleotide polymorphism (SNP) variants of the uridine diphosphate glucuronosyltransferase 1A1 (<i>UGT1A1</i>) gene have been studied as an important factor in neonatal hyperbilirubinemia (jaundice) severity. Specific ethnicities, including Asians, have certain SNPs that appear more frequently than others. <b>Aim:</b> To identify the most common SNPs in Indonesian neonates and their association with the severity of neonatal hyperbilirubinemia. <b>Methods:</b> Eighty-eight inborn and outborn jaundiced infants from three different hospitals (Bengkulu, Jakarta, Biak Papua) across Indonesia were enrolled in this cross-sectional study and their peak total serum bilirubin (TSB) levels assessed. SNP variant analyses of the TATAA box, promoter, and exon 1 regions of UGT1A1 gene from 78 of the 88 infants were carried out using the SNaPshot^R Multiplex Polymerase Chain Reaction (PCR) System followed by DNA sequencing. <b>Results:</b> We detected SNP variants <i>UGT1A1</i> ^* <i>28, UGT1A1</i> ^* <i>60, UGT1A1</i> ^* <i>93</i>, and <i>UGT1A1</i> ^* <i>6</i> in our population. Mean total serum bilirubin (TSB) was 14.59 ± 5.57 mg/dL. Bivariate analyses using delivery location, gestational age, birth weight, mother's age, and ethnicity were shown to be associated with moderate-to-severe hyperbilirubinemia (<i>p</i> < 0.05). None of the four SNPs appeared to be associated with moderate-to-severe hyperbilirubinemia. In multivariate analysis, however, only the "other ethnic group" (e.g., Chinese, Bengkulu, Papua, Bima) category showed an association with moderate-to-severe hyperbilirubinemia, with an odds ratio of 6.49 (95% CI 1.01-41.67; <i>p</i> < 0.05). <b>Conclusions:</b> We found that the <i>UGT1A1</i> ^* <i>60</i> is the most common SNP detected in neonates with hyperbilirubinemia in the Indonesian population. Interestingly, in Indonesia, <i>UGT1A1</i> polymorphisms do not appear to be associated with differences in the severity of hyperbilirubinemia.