G894T of nos3 gene polymorphism and resistant arterial hypertension in Uzbek population
Authors: Yusupova K H F , Masharipov S H M , Abdullaeva G J , Khamidullaeva G A , Zakirova D V , Abdullaev A A , Radjapova G M 
Published: November 2023

Abstract

Aim
To estimate the influence of G894T polymorphism of NOS3 gene on the risk of developing resistant arterial hypertension (AH) in the Uzbek population.

Materials and Methods
The study included 176 patients with AH I-III degree (ESH / ESC, 2018) of both sexes of Uzbek population. The mean age of the patients was 57.12 ± 11.03 years, the mean duration of AH was 9.58 ± 5.76 years. Resistant hypertension was defined in uncontrolled BP, even though ≥ 3 drugs of different classes were taken. Genotyping of the G894T polymorphism of NOS3 gene was performed using real-time PCR using gene-specific primers of allele-specific probes, followed by fluorescence detection of the corresponding alleles. Relative risk (RR) was calculated using genetic models. Calculations were performed using the online program "Calculator for calculating statistics in case-control studies". The results of all studies were considered statistically significant at p&lt;0.05.

Results
All patients were divided into two groups: group 1 - patients with resistant hypertension (cases, n=61) and group 2 - patients with controlled hypertension (controls, n=115). Among patients of group 1, the following distribution of the G894T polymorphism of the NOS3 gene was revealed: GG genotype - determined in 45.9% of patients, GT genotype - in 44.3%, TT genotype - 9.8%, χ2=22.770, p=0.000 . The allelic distribution showed the predominance of carriage of the G allele: G allele - 68.0%, T allele - 32.0%, χ2=30.311, p=0.000. Among patients of group 2, the allelic distribution was with a significant prevalence of the G allele: G allele in 80.9%, T allele in 19.1%, respectively, χ2=172.878, p=0.000. The ratio of GG:GT:TT genotypes was as follows: 67.8% : 26.1% : 6.1%, χ2=102.704, p=0.000. An analysis using genetic models of inheritance revealed a protective effect of the G allele G894T of the NOS3 gene polymorphism on the risk of developing resistant hypertension in the Uzbek population: among 115 patients with controlled hypertension of group 2, the G allele was significantly more common than in patients with resistant hypertension of group 1 (80.9%; χ² = 7.29 P=0.007; OR=0.50, 95% CI 0.30-0.83) and only 19.1% of patients had the T allele (χ²=P=0.007; OR=1.99 95% CI 1.20-3.28). The general model of inheritance demonstrated a significant accumulation of the GG genotype among patients of group 2 67.8% (χ² = 8.01; P = 0.02; OR = 0.40, 95% CI 0.21-0.76), while the GT genotype was less common in 26.1% cases and the TT genotype is even rarer in 6.1% of cases. Whereas in 1st group of patients GG and GT genotypes were found in the same ratio: 45.9%: 44.3%, respectively.

Conclusion
The results obtained indicate a significantly greater accumulation of the G allele G894T of NOS3 gene polymorphism among patients with controlled hypertension. Carrying the G allele and GG genotype G894T of NOS3 gene polymorphism is associated with a low risk of developing resistant hypertension in Uzbek population.