School of Life Sciences, Anhui University, Hefei, China.
Institute of Physical Science and Information Technology, Anhui University, Hefei, China.
Clin Appl Thromb Hemost. 2018 Dec;24(9_suppl):240S-247S. doi: 10.1177/1076029618805863. Epub 2018 Oct 18.
Our goal was to examine the associations of the 388A>G and 521T>C polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene with hepatic function, baseline lipid levels, and the lipid-lowering efficiency of simvastatin. We recruited 542 patients with hyperlipidemia. The 388A>G and 521T>C polymorphisms were genotyped. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST), Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured before and after an oral 20-mg dose of simvastatin. Individuals with the 388AA genotype had higher ALT and AST levels than those with the 388AG or 388GG genotypes (P = .037 and P = .002, respectively). Individuals with both the 388AA and the 521TT genotypes had the highest levels of ALT and AST (P = .001 and P = .001, respectively). Moreover, we divided all patients into normal and abnormal subgroups based on elevated ALT and AST values (≥ 40 U/L), participants in the abnormal subgroup had a higher frequency of the 388A/521T haplotype and a lower frequency of the 388G/521T haplotype compared to those in the normal subgroup. In addition, compared to 388G allele and 521C allele carriers, individuals with the 388G allele and 521TT genotype carriers had greater TC and LDL-C reduction in response to simvastatin after 4 weeks of treatment. Our conclusion suggests that the interaction between the SLCO1B1 388A>G and 521T>C polymorphisms could be an important genetic determinant of hepatic function and the therapeutic efficiency of simvastatin in Chinese patients with hyperlipidemia.
我们的目的是研究溶质载体有机阴离子转运蛋白 1B1（SLCO1B1）基因中的 388A>G 和 521T>C 多态性与肝功能、基线血脂水平以及辛伐他汀的降脂效率之间的关联。我们招募了 542 名高血脂患者。对 388A>G 和 521T>C 多态性进行了基因分型。测量了口服 20mg 辛伐他汀前后血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）、血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平。与 388AG 或 388GG 基因型相比，388AA 基因型个体的 ALT 和 AST 水平更高（P =.037 和 P =.002）。同时携带 388AA 和 521TT 基因型的个体的 ALT 和 AST 水平最高（P =.001 和 P =.001）。此外，我们根据 ALT 和 AST 值升高（≥40 U/L）将所有患者分为正常和异常亚组，异常亚组中 388A/521T 单倍型的频率较高，388G/521T 单倍型的频率较低。此外，与 388G 等位基因和 521C 等位基因携带者相比，携带 388G 等位基因和 521TT 基因型的个体在接受辛伐他汀治疗 4 周后，TC 和 LDL-C 的降低更为显著。我们的结论表明，SLCO1B1 388A>G 和 521T>C 多态性之间的相互作用可能是中国高血脂患者肝功能和辛伐他汀治疗效果的重要遗传决定因素。
