T-786C Polymorphism of the NOS3 Gene and Its Role in the Development of Renal Dysfunction in Patients of the Uzbek Population with Chronic Heart Failure-Uncorrected Proof

Objective: The aim of this study was to investigate the impact of the T-786C polymorphism of the NOS3 gene on the onset and progression of renal dysfunction in patients of the Uzbek population with chronic heart failure (CHF).

Method: The study included 200 patients of Uzbek nationality diagnosed with CHF. Among them, 110 patients had a glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m², while in 90 patients this indicator was lower. The control group consisted of 120 conditionally healthy donors of Uzbek nationality. Analysis of the NOS3 T-786C polymorphism was performed using commercially available test kits developed by NPF Litex LLC (Moscow, Russia) in accordance with the manufacturer’s standard protocol. Amplification of the polymorphic region of the NOS3 promoter was carried out using a Rotor-Gene Q thermal cycler (QIAGEN, Hilden, Germany). Polymerase chain reaction (PCR) was performed in a total volume of 25 µL under the following cycling conditions: initial denaturation at 95°C for 5 minutes; 35 cycles of denaturation at 95°C for 30 seconds, primer annealing at 60°C for 30 seconds, and DNA extension at 72°C for 1 minute; followed by a final extension at 72°C for 10 minutes. The resulting data were analyzed using the SPSS statistical package (IBM Corp., Armonk, NY, USA) and OpenEpi v9.2 (OpenEpi, Emory University, Atlanta, GA, USA).

Results: Differences were observed in the distribution of genotypic and allelic variations. In the main group, the frequency of the C allele was 35.5%, compared to 28.3% in the control group. Patients with eGFR < 60 mL/min/1.73 m² were more likely to have the C/C genotype (15.6% versus 10.8% in the control group). The T-786C polymorphism may exacerbate renal impairment by reducing NOS3 activity and lowering nitric oxide (NO) production.

Conclusion: The genetic variant C of the T-786C NOS3 polymorphism is associated with impaired renal function in patients with CHF.

Keywords: Chronic heart failure, clinical and humoral aspects, genetic aspects, renal dysfunction