Effect of Genetic Polymorphism of OATP-C (SLCO1B1) on Lipid-Lowering Response to HMG-CoA Reductase Inhibitors

Abstract

  The effect of genetic polymorphism of human organic anion transporting polypeptide C (OATP-C) on the lipid-lowering response to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors was assessed.
   A retrospective study was conducted on 66 patients who underwent treatment of hyperlipidemia with HMG-CoA reductase inhibitors in a municipal hospital in a community-based cohort of Ehime prefecture in the southern part of Japan. Plasma lipid concentrations before and after administration were analyzed in patients in relation to the 521T/C (Val-174→Ala) polymorphism in the OATP-C gene (TT: n=44 (66.7%), TC: n=20 (30.3%), CC: n=0 (0.0%), undetermined: n=2 (3.0%)). Total cholesterol level was significantly lowered after treatment with HMG-CoA reductase inhibitors in all patients (p<0.001); moreover, subjects with the 521C allele showed an attenuated total-cholesterol-lowering effect compared with those homozygous for the 521T allele (-22.3±8.7% vs. -16.5±10.5%, p<0.05).
   These data suggest that the 521T/C polymorphism of the OATP-C gene modulates the lipid-lowering efficacy of HMG-CoA reductase inhibitors.