Abstract
This study investigated the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms as possible genetic risk factors for the restenosis development in patients with drug-eluting stents. 113 participants had coronary artery disease and underwent stenting. The control group consisted of 62 individuals with intact coronary arteries. Patients were divided into two groups: with in-stent restenosis (ISR) and without it. The patients with ISR were classified into subgroups by the terms of the restenosis development and age. Real-time PCR and Restriction Fragment Length Polymorphism-PCR were used to genotype the study participants for RAAS gene polymorphisms. We found that the development of restenosis is generally associated with the minor A allele for renin (REN) rs2368564 and the major TT genotype for angiotensinogen (AGT) rs699. The heterozygous genotype for AGT rs4762 acts as a protective marker. A minor A allele for angiotensin II type 2 receptor (AGTR2) rs1403543 is associated with a risk of restenosis in people under 65 years old. Among patients with the early ISR, heterozygotes for angiotensin II type 1 receptor (AGTR1) rs5186 are more frequent, as well as A allele carriers for AGTR2 rs1403543. A minor homozygous genotype for REN rs41317140 and heterozygous genotype for aldosterone synthase (CYP11B2) rs1799998 are predisposed to the late restenosis. Thus, to choose the effective treatment tactics for patients with coronary artery disease, it is necessary to genotype patients for the RAAS polymorphisms, which, along with age and clinical characteristics, will allow a comprehensive assessment of the risk of the restenosis development after stenting.
Highlights
IntroductionOne of the most common medical approaches to the treatment of coronary artery disease (CAD) is the percutaneous coronary intervention (PCI) which became frequent due to high efficiency and safety of this procedure
Significant differences were found for three parameters, which were the occurrence of diabetes mellitus, the frequencies of multifocal atherosclerosis, and multivessel coronary artery disease
We found that the frequency of A allele and AA homozygotes for REN rs2368564 polymorphism was significantly higher in the group of patients with ISR, and the minor allele was associated with the development of in-stent restenosis in patients with stable coronary artery disease (CAD) after implantation of the drug-eluting stents (DES)
Summary
One of the most common medical approaches to the treatment of coronary artery disease (CAD) is the percutaneous coronary intervention (PCI) which became frequent due to high efficiency and safety of this procedure. Modern-day advances in pharmacotherapy and the device innovations over the last thirty years enhanced the benign outcomes of patients with unstable or multivessel CAD, and multiple co-morbidities, treated by PCI [1]. The advent of drug-eluting stents (DES) has revolutionized endovascular surgery, reducing the frequency of in-stent restenosis (ISR) from 20–40% to 6–12% [2]. The sharp rise in the total number of DES placements (e.g., more than one million procedures performed annually in the U.S.) has resulted in an increase in the absolute number of ISR cases
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