Kim Tae-Eun, Shin Dongseong, Gu Namyi, Jung Byung Hwa, Kim Jayoun, Cho Young Min, Yu Kyung-Sang, Cho Joo-Youn
Department of Clinical Pharmacology, Konkuk University Medical Center, Seoul, Korea.
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Basic Clin Pharmacol Toxicol. 2017 Sep;121(3):195-201. doi: 10.1111/bcpt.12826. Epub 2017 Jul 10.
Rosuvastatin is an HMG-CoA reductase inhibitor widely used for treating hypercholesterolaemia. We investigated whether genetic polymorphisms in solute carrier organic anion transporter 2B1 (SLCO2B1) affect the lipid-lowering effect of rosuvastatin in healthy adults with elevated low-density lipoprotein (LDL). This study included 18 volunteers with LDL levels above 130 mg/dL. Rosuvastatin (20 mg) was administered once a day for 8 weeks. Blood samples were drawn before and after the 8-week treatment to measure changes in lipid levels. The presence of single nucleotide polymorphisms (SNPs) of SLCO2B1 (c.935G>A and c.1457C>T), SLCO1B1 (c.521C>T, c.388A>G and c.-11187G>A) and ABCG2 (c.421C>A) was determined by genotyping. Responses to rosuvastatin were compared between wild-type and variant genotypes using permutation test on each polymorphism. In volunteers with SLCO2B1 c.935G>A (rs12422149) variant, rosuvastatin was less effective at lowering LDL (mean % decrease: GG 62.8% GA 50.6% AA 49.3%, p = 0.012) and apoprotein B (mean % decrease: GG 52.1% GA 42.8% AA 42.8%, p = 0.036). Regarding SLCO2B1 c.1457C>T (rs2306168) SNP, there was no significant difference between wild-type and variant genotypes. This study demonstrated that SLCO2B1 c.935G>A (rs12422149) polymorphism influenced the lipid-lowering effects of rosuvastatin in volunteers with hypercholesterolaemia.
瑞舒伐他汀是一种广泛用于治疗高胆固醇血症的HMG - CoA还原酶抑制剂。我们研究了溶质载体有机阴离子转运体2B1（SLCO2B1）的基因多态性是否会影响瑞舒伐他汀对低密度脂蛋白（LDL）升高的健康成年人的降脂效果。本研究纳入了18名LDL水平高于130mg/dL的志愿者。瑞舒伐他汀（20mg）每天服用一次，共服用8周。在8周治疗前后采集血样以测量血脂水平的变化。通过基因分型确定SLCO2B1（c.935G>A和c.1457C>T）、SLCO1B1（c.521C>T、c.388A>G和c.-11187G>A）以及ABCG2（c.421C>A）的单核苷酸多态性（SNP）的存在情况。使用每种多态性的置换检验比较野生型和变异基因型对瑞舒伐他汀的反应。在携带SLCO2B1 c.935G>A（rs12422149）变异的志愿者中，瑞舒伐他汀降低LDL（平均降低百分比：GG 62.8%、GA 50.6%、AA 49.3%，p = 0.012）和载脂蛋白B（平均降低百分比：GG 52.1%、GA 42.8%、AA 42.8%，p = 0.036）的效果较差。关于SLCO2B1 c.1457C>T（rs2306168）SNP，野生型和变异基因型之间没有显著差异。本研究表明，SLCO2B1 c.935G>A（rs12422149）多态性影响了高胆固醇血症志愿者中瑞舒伐他汀的降脂效果。
