ROLE OF THE T (-344) C POLYMORPHISM OF ALDOSTERONE SYNTHASE GENE CYP11B2 IN THE DEVELOPMENT OF CARDIORENAL SYNDROME IN PATIENTS WITH DIABETES MELLITUS

Abstract

Objective: To evaluate the role of the T (-344)C polymorphism of CYP11B2 gene in the development of cardiorenal syndrome (CRS) in diabetes mellitus (DM). Design and method: We examined 270 patients with type 1 and type 2 diabetes aged over 25 years. Control group included 60 healthy patients the same age. Renal function was assessed based on the levels of serum creatinine, cystatin C, eGFR, which was calculated according to the CKD-EPI formula, and albuminuria, which was assessed as albumin/creatinine ratio. All patients underwent molecular genetic analysis using deoxyribonucleic acid isolated from whole venous blood. Results: The frequency of carriage of the TT polymorphism of the CYP11B2 gene was significantly higher (47%) in the group of patients with DM than in the control group (26%). Carriers of the TT genotype had significantly high levels of homocysteine (10.5 [8.3;15.1] μmol/L) and FGF-23 (3.22 [0.77;7.60] pmol/L) as in DM group and in the control group (8.3 [7.54;10.9] μmol/l and 2.4 [2.19;2.6] pmol/l, respectively) than carriers of the CC genotype. The TT genotype was associated with the risk of developing CRS manifestations such as left ventricular hypertrophy (odds ratio (OR) 2.64; 95% CI (0.93–4.19), chronic heart failure (OR 4.26; 95% CI (2.26 - 8.06), subclinical atherosclerosis (OR 4.04; 95% CI (1.89 - 8.58), chronic kidney disease (CKD) (OR 10.77; 95% CI (3.56 - 32.61), and the CT genotype (OR 3.28; 95% CI (1.02 – 10.59) with CKD risk. Conclusions: There are pathogenetic association between the renin-angiotensin-aldosterone system, cardiovascular complications and a decrease renal function. Further research is needed for a deep understanding of the complex pathogenetic mechanisms of the development and progression of cardiovascular and renal pathology.