A1166C polymorphism of the angiotensin AT1 receptor (AT1R) gene alters endothelial response to statin treatment.

Background: The function of vascular endothelium is influenced by several factors: low-density lipoprotein (LDL) cholesterol, oxidative stress and the reninangiotensin system. Methods: We tested the hypothesis that polymorphisms A1166C of the angiotensin AT1 receptor (AT1R) gene, C242T and A640G of the pphox22 gene (p22 phox is an essential component of NADH/NADPH oxidases) and G894T of the endothelial nitric oxide (NO) synthase (eNOS) gene influence endothelial function and its reaction to statin treatment. In 44 patients with coronary artery disease or hypercholesterolemia (not on lipid-lowering treatment), lipid profile and endothelial function (brachial artery flow-mediated dilation, FMD) were measured at baseline and after treatment with statins for 8-12 weeks. All subjects were genotyped for the above-mentioned polymorphisms. Results: None of the polymorphisms significantly predicted baseline FMD. Patients with the C allele of A1166C showed smaller changes in FMD in comparison with patients with the AA genotype (-0.044±0.439% vs. 0.386±0.599%; p=0.016). None of the other polymorphisms significantly influenced changes in FMD. Conclusions: The C allele of AT1R A1166C is associated with significantly lower endothelial response to statin treatment.