Substantially Increased Plasma Coproporphyrin-I Concentrations Associated With OATP1B1*15 Allele in Japanese General Population

Abstract

Coproporphyrin-I (CP-I) in plasma is a sensitive and specific endogenous probe for phenotyping organic anion transporting polypeptides 1B (OATP1B, encoded by SLCO1B). A few small-scale studies suggested that plasma CP-I concentration is affected by OATP1B1 polymorphism, but detailed studies are lacking. In this large-scale study, we measured plasma CP-I concentrations in 391 subjects from the Japanese general population, and evaluated the relationship between plasma CP-I concentrations and OATP1B1 polymorphisms to further assess the utility of plasma CP-I concentrations as an endogenous OATP1B probe. Plasma CP-I concentrations were 0.45 ± 0.12, 0.47 ± 0.16, 0.47 ± 0.20, 0.50 ± 0.15, 0.54 ± 0.14, and 0.74 ± 0.31 ng/mL in participants with OATP1B1*1b/*1b (n = 103), *1a/*1b (n = 122), *1a/*1a (n = 40), *1b/*15 (n = 74), *1a/*15 (n = 41), and *15/*15 (n = 11), respectively, showing an ascending rank order with significant difference (P < 0.0001). Post hoc analysis revealed significant increases in plasma CP-I concentration in OATP1B1*1b/*15 (P = 0.036), *1a/*15 (P = 0.0005), and *15/*15 (P = 0.0003) groups compared with the OATP1B1*1b/*1b group. There was no significant difference among OATP1B genotypes in plasma concentration of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, a uremic toxin reported to decrease OATP1B activity in vivo. These findings confirm the utility of plasma CP-I concentrations as an endogenous biomarker for phenotyping of OATP1B activity. Plasma CP-I concentration is potentially useful for the study of drug-drug interactions via OATP1B or individual dose adjustment of OATP1B substrates.