Association of ABCC2 polymorphism and gender with high-density lipoprotein cholesterol response to simvastatin.

Abstract

The clinical benefits of lipid-lowering therapy with statins are widely recognized.However, the lipid-lowering efficacy of statins shows significant differences between individuals. ABCC2 has been demonstrated to contribute to the transmembrane transport of the substrate compounds. The ABCC2 SNPs may be important factors that affect individual differences in clinical drug response. The aim of this study was to evaluate the association of rs717620 of ABCC2 with treatment response to simvastatin in a Chinese Han population. A total of 318 subjects were medicated with simvastatin 20mg/day for 12 weeks after enrollment. Venous blood was obtained before and after simvastatin treatment for measurement of blood lipid profile. Subjects were classified into high-response and low-response groups depending on whether their lipid profile change was higher or lower than median change values. The ABCC2 SNP rs717620 was genotyped from blood samples with a snapshot assay. A total of 12 weeks of treatment with simvastatin significantly decreased low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TGs) and significantly increased high-density lipoprotein cholesterol (HDL-C; p < 0.05). In multivariate analysis, there were no significant genetic effects of SNP rs717620 on the incidence of high- or low-response patients among TC, TG and LDL-C groups. However, rs717620 A-allele and female gender are significantly associated with the risk of low-response of HDL-C elevation after simvastatin treatment. ABCC2 rs717620 and female gender may be related to the low-effect of simvastatin treatment on the HDL-C level in the Chinese Han population. Female Chinese patients with hyperlipidemia carrying rs717620 GA/AA genotypes might have reduced benefit from simvastatin treatment.