Assessment of The Effect of The A1166C Polymorphism of The AGTR1 Gene on The Formation of Comorbidity Associated with Cardiovascular Risk in patients with ankylosing spondylitis

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by damage to the axial skeleton, peripheral joints and periarticular apparatus, manifestation of systemic manifestations with predominant involvement of the vascular membrane of the eye, skin with the development of psoriasis and intestines. AU is characterized by an earlier onset of arterial hypertension (AH), as well as a higher level of cardiovascular risk (CVR) associated with AH. Endothelial dysfunction as the initial stage of the development of cardiovascular diseases (CVD) can occur due to the activation of the prohormone renin and high activity of angiotensin (Ang) II. Ang II is involved not only in the regulation of blood pressure, but also performs hematopoietic functions, mainly erythropoiesis and myelopoiesis. Several studies have shown the association of AGTR1 (1166A>C) angiotensin II type 1 receptor polymorphism with hypertension, vasoconstriction, and sodium retention in the body. Therefore, it is potentially important to evaluate the role of oligonucleotide polymorphism (SNP) A1166C of the AGTR1 gene in the clinical manifestation of AS, as well as its significance in the development of comorbid pathology and the formation of CVR, including hypertension. Aim : to evaluate the effect of the A1166C polymorphism of the AGTR1 gene on the development of comorbid pathology and the formation of CFS, including AH. Materials and methods : The study included 176 patients diagnosed with AS. Genotyping was carried out according to the A1166C polymorphism of the AGTR1 gene by the polymerase chain reaction method (PCR). The statistical analysis was carried out using the Kruskal-Wallis criterion. Results: Patients with the AA genotype had a higher BASMI (Bath Ankylosing Spondylitis Metrology Index) (p=0024, p1,3=0.023). CC homozygotes had lower levels of red blood cells (p=0.025, p2,3=0.02) and hemoglobin (p=0.031, p2,3=0.042), while AA genotypes had lower platelet counts (p=0.0001, p1,3=0.001). Higher glucose levels were recorded in CC homozygotes (p=0,0001, p1,3=0,001, p1,2=0,025), triglycerides — in heterozygotes AC (p=0.038). The highest incidence of enthesitis was recorded for patients with the CC genotype (p2,3=0.006, p=0.015). High incidence of hypertension (p1,2=0.05, p=0.025), dyslipidemia (p1,2=0.012, p2,3=0.006, p=0.031) was found in heterozygotes of AC. Diabetes mellitus was detected only among patients with the CC genotype(p1,3=0.007, p=0.017). Kidney damage was more often detected in carriers of the A allele (p1,3=0.015, p2,3=0.004, p=0.023). Statistical differences were found in the frequency of detection of individual degrees of hypertension (p=0.0001): in heterozygotes of AC — 2 (AA 26 (27.1 %); AC 4 (33.3 %); CC 14 (24.1 %)) and grade 3 (AA 0 (0.0 %) versus AC 2 (16.7 %) CC 0 (0.0 %), p1,2<0.001, p2,3=0.004). Conclusion : The obtained results reveal a wide range of functions of the SNP 1166A>C of the AGTR1 gene, extending beyond participation in the formation of hypertension, and include the regulation of hematopoiesis, metabolic parameters, glucose and lipids in particular, and the formation of comorbid pathology in the form of diabetes mellitus, dyslipidemia, kidney pathology in patients with AS, which determines the potential and feasibility of genotyping patients with AS with the identification of SNPs in order to personalize approaches to pharmacotherapy of AS and monitoring these indicators in the presence of a risk of developing conditions associated with this SNP.