Abstract
ObjectiveIt has been established that genetic factors play a substantial role in the development of neonatal hyperbilirubinemia. The population of Indonesia and other Southeast Asian countries has similar, yet different genetic makeup compared to the rest of Asia. Aside from UGT1A1, variants of SLCO1B1 have also been known to contribute to the severity of neonatal hyperbilirubinemia in Asian populations. Since there has been no report on SLCO1B1 polymorphism in relation with hyperbilirubinemia in Indonesia, this study aims to explore incidence of SLCO1B1*1B polymorphism in Indonesia based on 3 hospitals from different provinces and population, and their association with hyperbilirubinemia severity.MethodsOur study included 88 neonates with mild and moderate-severe hyperbilirubinemia from 3 NICU in hospitals representing homogenous and heterogenous populations: Biak General Hospital Papua, Cipto Mangunkusumo Hospital (Jakarta), and M Yunus Hospital (Bengkulu). We collected samples between November 2016 and September 2017. DNA was obtained from existing samples of the patients from previous studies and were subjected to Polymerase Chain Reaction – Restriction Fragment Length Polymorphism (PCR-RFLP). We analyzed the *1B variant located in exon 5 of SLCO1B1 with TaqI restriction endonuclease. Clinical, demographic, and laboratory data was also collected from medical records and parents’ interviews.ResultsThe most dominant variant of SLCO1B1*1B in our population is the homozygous G/G (68.18%), followed by heterozygous A/G (26.14%), and wild type A/A (5.68%). The heterozygous A/G had an Odds Ratio (OR) of 0.73 (95% CI 0.10–5.2) and homozygous G/G with OR of 0.51 (95%CI 0.08–3.27), both were not significant. Genotypic distribution across the different centers were also similar and not significant. The significant risk factors for moderate-severe hyperbilirubinemia were the population the neonate originated from (p = < 0.001) and the delivery location (p = 0.001), while SLCO1B1*1B was not associated with the different severity of hyperbilirubinemia.ConclusionsSLCO1B1*1B is not associated with higher bilirubin levels among neonates with hyperbilirubinemia in Indonesia. Further study is needed to find other potentially important genetic polymorphisms in the development of severe hyperbilirubinemia in Indonesia.
Highlights
Neonatal hyperbilirubinemia occurs in about 60% of all term infants [1]
The heterozygous A/G had an Odds Ratio (OR) of 0.73 and homozygous G/G with OR of 0.51 (95%Confidence Interval (CI) 0.08–3.27), both were not significant
The significant risk factors for moderate-severe hyperbilirubinemia were the population the neonate originated from (p = < 0.001) and the delivery location (p = 0.001), while SLCO1B1*1B was not associated with the different severity of hyperbilirubinemia
Summary
Neonatal hyperbilirubinemia (jaundice) occurs in about 60% of all term infants [1]. In general, most of the increase in bilirubin levels is physiological and usually will improve by the end of the first week of life. The most commonly-studied gene is the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) that is closely associated with Crigler-Najjar’s syndrome type I and II, and Gilberts syndrome These conditions are frequently found in Caucasian and African populations [7, 8]. SLCO1B1 (solute carrier organic anion transporter family member 1b1) encodes the solute carrier organic anion transporter family member 1B1 and is responsible for the absorption of unconjugated and conjugated bilirubin in the liver This gene, located in chromosome 12p12, consists of 15 exons (1 coding exon and 1 non-coding exon) and 14 introns, as well as containing 2073 nucleotides in the gene-coding area [9]. The most frequent polymorphisms found in this gene are SLCO1B1*1B (388A > G), SLCO1B1*4 (463C > A), and SLCO1B1*5 (521 T > C), and the most commonly associated with hyperbilirubinemia is the SLCO1B1*1B (388A > G) [9, 11,12,13]
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