In subgroup analyses based on ethnicity, no significant associations were found in white, Asian, Brazilian, and Malaysian populations, but a low risk was found

in Chinese neonates. Three case-control studies from three countries assessed the association between the SLCO1B1 463 C>A mutation and neonatal hyperbilirubinemia. No carriage of the C to A substitution at nucleotide 463 was detected among three studies, and only one study of American infants reported the variant SLCO1B1 at nt 463 in hyperbilirubinemic and in control infants (0.156 and 0.155, respectively), with no statistically significant difference between the groups. Egger’s test provided no evidence for funnel plot asymmetry in the comparison of the SLCO1B1 388 G>A and 521 T>C DNA Damage inhibitor mutations and neonatal hyperbilirubinemia. Three studies focused on the relationship between the SLCO1B1 463 C>A mutation and neonatal hyperbilirubinemia: two studies did not detect a carriage of the C to A substitution, and one study showed a non-significant increase in the risk of

neonatal hyperbilirubinemia. No significant inter-study heterogeneity was observed in the analyses. Therefore, it is believed that the results of the present meta-analysis are reliable. In the nine included studies, which analyzed the association between the SLCO1B1 388 G>A mutation and neonatal hyperbilirubinemia, only three studies from China showed a positive relationship.13, find more 14 and 15 In five included studies that analyzed the association between the SLCO1B1 521 T>C

mutation and neonatal hyperbilirubinemia, only one study from China showed a negative relationship.12 In other populations, no statistically significant difference was observed. The genetics of racial differences might explain the variability in prevalence of neonatal hyperbilirubinemia among different ethnic groups. An in vitro expression study demonstrated that SLCO1B1 388 G>A variations are consistently associated with reduced transport activity of SLCO1B1. 21 Evidence suggests that transient hyperbilirubinemia may be caused by potent SLCO1B1 inhibitors, such as indinavir, saquinavir, Carnitine dehydrogenase cyclosporine A, and rifamycin. 22 Following rifampicin administration (450 mg/day) for five consecutive days, serum bilirubin levels were significantly increased, and unconjugated bilirubin, direct bilirubin, and total bilirubin levels were increased by 24.9%, 31.5%, and 26.8%, respectively. 23 Thus, modulation of the transporting activity of SLCO1B1 could alter the transportation and subsequent elimination of serum bilirubin. The SLCO1B1*1B (C388 G–C521T) haplotype has been associated with increased OATP1B1 transport activity in vitro in studies performed with bromosulfophthalein and estrone-3-sulfate.