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

Abstract

Background: Single nucleotide polymorphism (SNP) variants of the uridine diphosphate glucuronosyltransferase 1A1 ( UGT1A1 ) 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. Aim: To identify the most common SNPs in Indonesian neonates and their association with the severity of neonatal hyperbilirubinemia. Methods: 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. Results: We detected SNP variants UGT1A1 * 28, UGT1A1 * 60, UGT1A1 * 93 , and UGT1A1 * 6 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 ( p < 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; p < 0.05). Conclusions: We found that the UGT1A1 * 60 is the most common SNP detected in neonates with hyperbilirubinemia in the Indonesian population. Interestingly, in Indonesia, UGT1A1 polymorphisms do not appear to be associated with differences in the severity of hyperbilirubinemia.

Clinical characteristics influence cultivable-bacteria composition in the meconium of Indonesian neonates

“…The use of certain antibiotics (e.g., ceftriaxone) may displace bilirubin from its serum albumin-binding site, resulting in the progression of hyperbilirubinemia [ 29 ]. As reported previously, clinical risk factors of older gestational age and greater birth weight show a significant association with a lower incidence of hyperbilirubinemia [ 30 ]. Hypothyroid is also one risk factor known to influence hyperbilirubinemia, but from the neonatal screening, none of our samples were found to have abnormal thyroid results [ 31 ].…”

Effects of variation status and enzyme activity for UDP-glucuronosyltransferase 1A1 gene on neonatal hyperbilirubinemia

“…16e18, 20,22,23 Therefore, this study may provide important references for Asian populations. Second, the further factor for the development of hyperbilirubinemia, the variation at nucleotide À3279 (T > G) (UGT1A1)60, rs4124874) in the UGT1A1 gene, 11,25 was ignored. This SNP will be examined in our further study on neonatal hyperbilirubinemia.…”

Association of UGT1A1*6 polymorphism with irinotecan-based chemotherapy reaction in colorectal cancer patients: a systematic review and a meta-analysis

“…Studies have indicated an association between UDP-glucuronosyltransferase-1A1 (UGT1A1) genetic polymorphisms and IRI-induced toxicity. UGT1A1 gene concludes many SNPs [ 25 , 26 ], and SNPs in candidate gene significantly associated with transcription or translation or regulation [ 27 ]. UGT1A1*28 is a member of family in SNPs of UGT1A1 gene, previous meta-analysis evaluated the impact of UGT1A1*28 polymorphisms with IRI-induced toxicity, and demonstrated UGT1A1*28 polymorphisms may be considered as a marker of IRI-induced toxicity in chemotherapy of cancer [ 28 ].…”