JOURNAL ARTICLE

Effect of SLCO1B1 polymorphism on the plasma concentrations of bile acids and bile acid synthesis marker in humans

Xiaoqiang Xiang, Yi Han, Mikko Neuvonen, Marja K Pasanen, Annikka Kalliokoski, Janne T Backman, Jouko Laitila, Pertti J Neuvonen, Mikko Niemi
Pharmacogenetics and Genomics 2009, 19 (6): 447-57
19387419

BACKGROUND AND OBJECTIVE: Organic anion transporting polypeptide 1B1 (OATP1B1, encoded by SLCO1B1) is a sinusoidal influx transporter of human hepatocytes. Our aim was to characterize the role of OATP1B1 in the hepatic uptake of bile acids in vivo.

METHODS: Fasting blood samples were drawn from 24 healthy volunteers with SLCO1B1 c.388AA-c.521TT (*1A/*1A) genotype, eight with c.388GG-c.521TT (*1B/*1B) genotype, 24 with c.521TC genotype, and nine with c.521CC genotype. Plasma concentrations of 15 endogenous bile acids, their synthesis marker, and cholesterol were determined by liquid chromatography-tandem mass spectrometry.

RESULTS: The concentrations of ursodeoxycholic acid, glycoursodeoxycholic acid, chenodeoxycholic acid, and glycochenodeoxycholic acid were approximately 50-240% higher in individuals with the SLCO1B1 c.521CC, c.521TC, or c.388AA-c.521TT genotype than in those with the c.388GG-c.521TT genotype (P<0.05), with the largest differences seen between the c.521CC and c.388GG-c.521TT individuals. The concentration of tauroursodeoxycholic acid was approximately 120% higher in individuals with the c.521TC genotype and that of taurochenodeoxycholic acid 110% higher in individuals with the c.521CC or c.521TC genotype than in those with the c.388GG-c.521TT genotype (P<0.05). The cholic acid concentration was approximately 30% higher in individuals with the c.521CC or c.388AA-c.521TT genotype than in those with the c.388GG-c.521TT genotype (P<0.05), but its conjugates remained unaffected by the genotype. The bile acid synthesis marker 7alpha-hydroxy-4-cholesten-3-one/cholesterol concentration ratio was 62 or 45% higher in the c.388AA-c.521TT participants than in the c.388GG-c.521TT or c.521TC participants, respectively (P<0.05).

CONCLUSION: SLCO1B1 polymorphism considerably affects the disposition of several endogenous bile acids and bile acid synthesis marker, indicating that OATP1B1 plays an important role in the hepatic uptake of bile acids in vivo in humans.

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