Association of lipids' metabolism disorders with aldosterone synthase CYP11B2 (-344C/T) gene polymorphism in hypertensive patients depending on glomerular filtration rate

Abstract

Abstract. The cytochrome 11B2 aldosterone synthase gene (CYP11B2) one of the possible encoding genes that relates to changes of aldosterone and blood pressure regulation. The aim is to analyse the lipids profile changes in arterial hypertensive patients (EAH) depending on glomerular filtration rate (GFR) and gene CYP11B2 (-344C/T) polymorphism. One-hundred hypertensive patients with hypertensive-mediated target-organ damaging (2nd stage), moderate, high or very high cardiovascular risk were enrolled in the case-control study. Mean age 59.87±8.02 y.o. Chronic Kidney Disease (CKD) was diagnosed in 29 persons according to the National Kidney Foundation recommendations (2012) after glomerular filtration rate (GFR) decline <60 ml/min/1,73m2 for ≥3 months (measured by CKD-EPI equations). Lipids profile assessed by total cholesterol level (TC), triglycerides (TG) and low / high density level cholesterol (LDL-C, HDL-C) in serum. Also, calculated waist-hip ratio (WHR) for abdominal obesity evaluation. Control group included 48 practically healthy persons of relevant age. Gene's nucleotide polymorphism CYP11B2 (-344C/T) was examined by polymerase chain reaction. TC, LDL-C level in hypertensive patients do not relate directly to polymorphic variants of CYP11B2 (rs1799998) gene. Though, dyslipidemia is more intensively manifested in the Т-allele carriers by elevation of TG and atherogenic index (AI) 22.61-56.21% (p<0.01) as much, with lower HDL-C concentration – by 12.23% (р=0.043) and 12.95% (p=0.039), respectively, particularly in men by 25.84 (p=0.031) and 35.76% (p=0.042) higher than in women. CKD evolution in hypertensive patients follows by higher TC, TG and LDL-C that causes an atherogenic index increase (AI) by 13.54% (p=0.028). Polymorphic site of CYP11B2 (rs1799998) gene is associated with TG and AI elevation in general population (F=13.98 and F=13.25; p<0.001), both in women (F=22.99 and F=15.21; p<0.001) and men particularly (F=5.09; p=0.018 and F=4.44; p=0.027) and reduced HDL-C content (F=5.28; p=0.007), especially in men (F=9.57; p=0.001). Furthermore, it associates with WHR increase (F=13.09; p=0.003), especially in the ТТ-genotype carriers' men (F=12.74; p<0.001). Polymorphic site of CYP11B2 (rs1799998) gene associates with dyslipidemia: TG and AI elevation, as well as WHR increase in general population, particularly in ТТ-genotype carriers' men. CKD in hypertensive patients is more related to lipids misbalance, than polymorphic site of CYP11B2 (rs1799998) gene.