SLCO1B1 c.388A > G variant incidence and the severity of hyperbilirubinemia in Indonesian neonates

Abstract

Objective It 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. Methods Our 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 Taq I restriction endonuclease. Clinical, demographic, and laboratory data was also collected from medical records and parents’ interviews. Results The 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. Conclusions SLCO1B1*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.

Associations between UGT1A1 and SLCO1B1 polymorphisms and susceptibility to neonatal hyperbilirubinemia in Thai population

“…However, the data from our study indicates that there were no statistically significant differences in risk factor of neonatal hyperbilirubinemia and SLCO1B1 388 A > G variant. Similar to Amandito R, et al [ 26 ], demonstrated that there was no statistically significant differences between occurrence of SLCO1B1 388 A > G and hyperbilirubinemia in newborns. In SLCO1B1 521 T > C variant, there was a significant correlation between hyperbilirubinemia and SLCO1B1 521 T > C ( P = 0.041).…”

Molecular Genetic Screening of Neonatal Intensive Care Units: Hyperbilirubinemia as an Example

“… 19 , 20 For instance, SLCO1B1 polymorphism, a gene encoding OATP2, is associated with jaundice, but such association varies across regions and populations. For the Chinese population, 388G>A and 521T>C mutations of SLCO1B1 are associated with an increased and decreased risk of neonatal jaundice, respectively, 21 , 22 but no such correlation is found in Indonesia, 23 white, Thai, Brazilian or Malaysian populations. 24 Some studies have shown that HO-1 gene polymorphism is associated with the risk of jaundice.…”

Risk factors for exchange transfusion in neonates with unconjugated hyperbilirubinemia: A tertiary care hospital study.

“…Despite concerted efforts to identify neonates at risk of pathological hyperbilirubinemia (HB), this pattern of hospitalization continues unabated. 1 Approximately 60% of term infants experience neonatal hyperbilirubinemia, with most cases representing physiological bilirubin increases that typically resolve within the first week of life. However, when serum total bilirubin (STB) levels surpass 5 mg/dL, visible jaundice may ensue, particularly in preterm infants, where the incidence escalates to 80%.…”