ALDOSTERONE SYNTHASE CYP11B2 (-344C/T) GENE POLYMORPHISM INFLUENCES RISK OF CHRONIC KIDNEY DISEASE IN PATIENTS WITH ARTERIAL HYPERTENSION

Abstract

Objective: Renin-angiotensin aldosterone system plays a major role in blood pressure regulation. Aldosterone, synthesized in the adrenal cortex by aldosterone synthase is encoded by the cytochrome 11B2 aldosterone synthase gene (CYP11B2). The aim of the study was to analyze the association of aldosterone synthase gene (CYP11B2) biallelic polymorphism (-344C/T) with Chronic Kidney Disease (CKD) in patients with essential arterial hypertension (EAH) in West-Ukrainian population. Design and method: One-hundred subjects with EAH and target-organ damaging (2nd stage), moderate, high or very high cardiovascular risk were involved in the case-control study. Among them 79.0% (79) females and 21.0% (21) males, mean age 59.87 ± 8.02 yo; disease duration from 6 to 25 years. CKD was determined by the National Kidney Foundation recommendations (Kidney Disease: Improving Global Outcomes (KDIGO), 2012) after glomerular filtration rate (GFR) decline < 60 ml/min/1.73sq.m for over 3 months (by Cockroft-Gault formula and CKD-EPI for Cystatin-C and Creatinine serum levels depending on gender). CKD was diagnosed in 29 persons. All enrolled / screened patients signed the Informed Consent to participate in the research. Control group included 48 practically healthy persons of relevant age. Gene polymorphism of aldosterone synthase gene CYP11B2 (-344C/T) was examined by polymerase chain reaction (PCR). Results: The probability of EAH in observed population increased 1.49 times in T-allele carriers of CYP11B2 gene, but only in females [OR = 1.90; 95%CI:1.02–3.54; p = 0.029], with contrary decreasing in C-allele women (p = 0.041). No relevant dependences were observed in hypertensive males. Also T-allele increased probability of CKD (GFR< 60 ml/min/1,73m2) in hypertensive population 1.48 times [OR = 1.86; 95%CI:1.01–3.58; p = 0.049], especially in T-allele females 1.53 times [OR = 6.51; 95%CI:1.39–30.60; p = 0.007] with low CKD risk in T-allele males [OR = 0.15; 95%CI:0.03–0.72; p = 0.009], respectively. Some predictors like DM2, the 2nd and 3rd grades of Obesity, and the 3rd grade level of Blood Pressure elevation escalated the risk of CKD 2.4, 2.08–2.32 and 2.91 times, accordingly (p< 0.05). Conclusions: Aldosterone synthase gene CYP11B2 (-344C/T) is associated with EAH. T-allele increased risk of CKD in hypertensive population, especially in females.