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.
Kiliszek
Marek
M
Department of Cardiology, Medical University of Warsaw, Warsaw, Poland. kiliszek@amwaw.edu.pl
Burzyńska
Beata
B
Styczyński
Grzegorz
G
Maciag
Monika
M
Rabczenko
Daniel
D
Opolski
Grzegorz
G
D000328:Adult; D000368:Aged; D003327:Coronary Disease / Q000235:genetics* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D044140:Receptor, Angiotensin, Type 1