Effect of genetic polymorphism of OATP-C (SLCO1B1) on lipid-lowering response to HMG-CoA reductase inhibitors.
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.
Tachibana-Iimori
Rieko
R
Department of Geriatric Medicine, Ehime University School of Medicine, 454 Shitsukawa, Tohon-shi, Ehime 791-0295, Japan.
Tabara
Yasuharu
Y
Kusuhara
Hiroyuki
H
Kohara
Katsuhiko
K
Kawamoto
Ryuichi
R
Nakura
Jun
J
Tokunaga
Katsushi
K
Kondo
Ikuko
I
Sugiyama
Yuichi
Y
Miki
Tetsuro
T
D000368:Aged; D000483:Alleles; D002784:Cholesterol / Q000097:blood; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007564:Japan; D008055:Lipids / Q000097:blood; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008055:Lipids; D027381:Liver-Specific Organic Anion Transporter 1; D004247:DNA; D002784:Cholesterol