The cytochrome 11B2 aldosterone synthase gene rs1799998 single nucleotide polymorphism determines elevated aldosterone, higher blood pressure, and reduced glomerular filtration, especially in diabetic female patients.
OBJECTIVE
The cytochrome 11B2 aldosterone synthase gene (CYP11B2) that links to aldosterone synthase enzyme synthesis changes and blood pressure regulation is of particular interest among the renin-angiotensin-aldosterone system encoding genes.


METHODS
One-hundred hypertensive patients with target-organ damaging (2nd stage), moderate, high or very high cardiovascular risk were involved in the case-control study. Mean age was 59.87±8.02 years. Diabetes Mellitus type 2 (DM2) was in 28 persons. 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). Aldosterone, cystatin-C, and creatinine levels were measured in serum. Control group included 48 practically healthy persons of relevant age. Gene's nucleotide polymorphism CYP11B2 (-344C/T) was examined by polymerase chain reaction.


RESULTS
CKD evolution in hypertensive patients followed by higher systolic and diastolic blood pressure (SBP, DBP) values increased creatinine, cystatin-C, and aldosterone serum concentrations by 28.76%, 28.41% and 29.43% (р<0.05), respectively. Polymorphic site of CYP11B2 (rs1799998) gene is associated with SBP and DBP increase (p<0.05), reduced GFR preferably calculated by CKDEPI-cystatin C (F=10.79-14.45; p<0.001) and elevated aldosterone content (F=55.84; p<0.001), creatinine and cystatin-С as well (F=4.16-5.08; p<0.05) mainly in the ТТ-genotype female carriers (p<0.001). Hypertensive women with DM2 demonstrated stronger relations of CYP11B2 gene polymorphic site with the increased aldosterone content (F=47.52; p<0.001), than women without DM2 (p<0.001) and male patients (p=0.014).


CONCLUSIONS
Genetic variations involving CYP11B2 might influence the kidney function, hypertension course, and severity via aldosterone secretion upregulation.
['Sydorchuk|Larysa|L|', 'Dzhuryak|Valentina|V|', 'Sydorchuk|Andrii|A|', 'Levytska|Svitlana|S|', 'Petrynych|Volodymyr|V|', 'Knut|Ruslan|R|', 'Kshanovska|Anna|A|', 'Iftoda|Oksana|O|', 'Tkachuk|Olexii|O|', 'Kyfiak|Petro|P|', 'Popovich|Andrii|A|', 'Khomko|Oleh|O|', 'Sydorchuk|Ruslan|R|']
D000328:Adult D000368:Aged D000450:Aldosterone D001794:Blood Pressure D016022:Case-Control Studies D019405:Cytochrome P-450 CYP11B2 D003924:Diabetes Mellitus, Type 2 D003928:Diabetic Nephropathies D005260:Female D020022:Genetic Predisposition to Disease D005919:Glomerular Filtration Rate D006801:Humans D006973:Hypertension D008297:Male D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D012084:Renin-Angiotensin System
aldosterone diabetes hypertension chronic kidney disease CYP11B2 (rs1799998) gene