AGT rs699 and AGTR1 rs5186 gene variants are associated with cardiovascular-related phenotypes in atherosclerotic peripheral arterial obstructive disease.

Abstract

Peripheral arterial diseases (PAD) refer to the arterial diseases other than coronary arteries and the aorta. Atherosclerosis is the major cause of PAD. Renin angiotensin aldosterone system (RAAS)-related genes were associated with cardiovascular diseases. Angiotensin II is the pro-inflammatory, proliferative and vasoconstrictor effector of RAAS in the vascular system. In this study, we aimed to investigate whether the effects of the angiotensinogen (AGT) rs699 (M268T), angiotensin-converting enzyme (ACE) I/D (rs1799752), angiotensin II receptor type 1 (AGTR1) (A1166C) rs5186, and angiotensin II receptor type 2 (AGTR2) rs35474657 variants were associated with PAD etiology due to atherosclerotic involvement of aorta-iliac and femoro-popliteal artery occlusions. AGT rs699, AGTR1 rs5186, ACE I/D (rs1799752), AGTR2 rs35474657 gene variants were determined by real-time polymerase chain reaction (RT-PCR) in 63 PAD patients (33 femoro-popliteal, 30 aorta-iliac) and 70 healthy controls. Although there was no significant relationship in the genotype frequencies of AGT rs699, AGTR1 rs5186, ACE I/D (rs1799752), and AGTR2 rs35474657 variants between PAD and control groups (p > 0.05), AGT rs699 TT genotype was significantly associated with fasting glucose (p = 0.023) in PAD patients. Besides, CC genotype of rs699 was significantly related with HDL-cholesterol levels (p = 0.020) in PAD group. Furthermore, AGTR1 rs5186 CC genotype carriers demonstrated significantly higher LDL-cholesterol (p = 0.034) and triglycerides levels (p = 0.007). This report is the first to show an association between RAAS-related gene variants and their relation with the biochemical characteristics of PAD and suggests that RAAS-associated gene variants may have significant roles in cardiovascular related phenotypes of PAD patients.