Effect of Cytochrome P450 7A1 (CYP7A1) Polymorphism on Lipid Responses to Simvastatin Treatment.

BACKGROUND

Identifying patients with high risk of low response to statin therapy is important for optimization of lipid-lowering therapy. Cholesterol 7α-hydroxylase, a rate-limiting enzyme encoded by cytochrome P450 7A1 (CYP7A1) gene, is considered to be associated with statin efficacy. This study aimed to investigate the association between a novel CYP7A1 single nucleotide polymorphism rs3824260 and statin treatment response for hypercholesteremic patients in Chinese Han population.

METHODS

A total of 336 subjects were prescribed with simvastatin for 12 weeks after enrollment. Plasma lipid parameters were measured at enrollment and after 12-week simvastatin treatment separately. Subjects were classified into high- and low-response groups depending on their total cholesterol, low-density lipoprotein cholesterol (LDL-C) and TG changes and increase or reduction groups according to their high-density lipoprotein cholesterol (HDL-C) levels changing after simvastatin treatment. The CYP7A1 rs3824260 was genotyped from blood samples with a SNaPshot assay.

RESULTS

At baseline, the LDL-C level and TG level were significantly higher in the AA genotype, while the HDL-C level was significantly higher in the GG genotype of CYP7A1 rs3824260. Patients carrying AA genotype are at an increased risk of low response for LDL-C reduction (odds ratio = 2.295, 95% confidence interval = 1.164-4.524, P = 0.016). Furthermore, the GG genotype of rs3824260 was significantly associated with a high risk of HDL-C reduction response after simvastatin therapy (odds ratio = 2.240, 95% confidence interval = 1.137-4.413, P = 0.025).

CONCLUSIONS

The CYP7A1 gene polymorphism rs3824260 is related to inappropriate response of simvastatin treatment for hypercholesterolemia patients in Chinese Han population.