1. Elevated serum bilirubin levels are caused mainly by liver diseases, 
haematolysis, genetic defects and drug intake. Unconjugated bilirubin (UCB) is 
taken up into hepatocytes by human organic anion transporting polypeptide 1B1 
(OATP1B1; encoded for by the SLCO1B1 gene). The present study was performed to 
determine the association between SLCO1B1 gene polymorphisms and serum bilirubin 
levels in vivo. Moreover, the effects of administration of low-dose rifampicin 
on serum bilirubin levels in different SLCO1B1 genotypes was examined. 2. Serum 
bilirubin levels were examined in 42 healthy volunteers who had been analysed 
for SLCO1B1 genotype (seven, 13, 14 and eight with SLCO1B1 genotypes *1a/*1a, 
*1b/*1b, *1b/*15 and *15/*15, respectively). Among them, 24 subjects (seven, 
seven, eight and two with SLCO1B1 genotypes *1a/*1a, *1b/*1b, *1b/*15 and 
*15/*15, respectively) were selected to participate in an open-label, two-phase 
clinical trial. Each was given 450 mg rifampicin orally once daily at 2000 hours 
for 5 consecutive days. Serum bilirubin concentrations at 0800 hours on the 1st 
and 6th days were compared between the different SLCO1B1 genotypes. 3. In the 42 
volunteers, the mean (+/-SD) serum UCB in both SLCO1B1*1b/*15 and *15/*15 groups 
was significantly higher than that in the SLCO1B1*1b/*1b group (11.07 +/- 2.31, 
13.01 +/- 3.87 and 8.21 +/- 2.68 micromol/L, respectively; P = 0.009 and P < 
0.001). Total bilirum (T.BIL) in both the SLCO1B1*1b/*15 and *15/*15 groups was 
significantly higher than that in the SLCO1B1*1b/*1b group (16.69 +/- 4.09, 
20.71 +/- 5.12 and 13.06 +/- 5.12 micromol/L, respectively; P = 0.029 and P < 
0.001). The direct bilirubin (D.BIL) in the SLCO1B1*15/*15 group was 
significantly higher than that in the SLCO1B1*1b/*1b group (7.69 +/- 1.81 vs 
4.85 +/- 1.81 micromol/L, respectively; P = 0.001). Rifampicin significantly 
increased UCB, T.BIL and D.BIL concentrations in 24 healthy volunteers (17.68 
+/- 5.96 vs 13.95 +/- 4.44 micromol/L (P = 0.040), 5.72 +/- 2.01 vs 4.35 +/- 
1.50 micromol/L (P = 0.028) and 12.00 +/- 4.26 vs 9.61 +/- 3.15 micromol/L (P = 
0.035), respectively). However, the extent of the increase in serum bilirubin 
caused by 450 mg rifampicin for 5 days was not affected by SLCO1B1 genotype. 4. 
Genetic polymorphism in SLCO1B1 is a major determinant of interindividual 
variability in the serum bilirubin level. SLCO1B1*15 carriers had higher 
baseline serum UCB, T.BIL and D.BIL levels compared with subjects with the 
SLCO1B1*1a/*1a and SLCO1B1*1b/*1b genotypes. SLCO1B1*15/*15 homozygotes are more 
susceptible to hyperbilirubinaemia. Serum bilirubin levels could be increased by 
low-dose rifampicin administration, but the extent of the increase was not 
associated with SLCO1B1 genotype.