Association of AGT (T704C) and NOS3 (G894T) Gene Polymorphisms with Treatment-Resistant Hypertension in the Uzbek Population

Abstract

The aim of our study was to assess the effect of polymorphic markers of the AGT T704C (M235T) rs699 and NOS3 G894T (Glu298Asp) rs1799983 SNPs on the risk of the development of treatment-resistant hypertension (TRH). Methods and Results: The study included 178 patients (mean age of 56.67±11.12 years) with AH Grades 1-3 (ESC/ESH, 2018), who were on outpatient treatment at the Republican Specialized Scientific and Practical Medical Center for Cardiology. Genomic DNA samples were isolated from the peripheral blood leukocytes by using the DiatomТМ DNA Prep 200 Kit (Isogen Laboratory LLC, Moscow, Russia) according to manufacturer`s protocol. A multiplex RT-PCR assay was used to detect the AGT T704C (M235T) rs699 SNP and NOS3 G894T (Glu298Asp) rs1799983 SNP. We studied the distribution of the AGT T704C (M235T) rs699 polymorphism in 61 Uzbek patients with TRH (cases) and 117 Uzbek patients with non-TRH (controls) (Group 1) and the distribution of the NOS3 G894T (Glu298Asp) rs1799983 polymorphism in 61 Uzbek patients with TRH (cases) and 115 Uzbek patients with non-TRH (controls) (Group 2). Our results indicate a significantly greater accumulation of the C allele and CC genotype of the AGT T704C (M235T) rs699 SNP among TRH patients than among patients with non-TRH. We found a significant association between the AGT T704C (M235T) rs699 SNP and the risk of TRH under the multiplicative genetic model (C vs. T : OR=1.85, 95% CI: 1.17-2.92, P=0.006), additive model (CC vs.TT vs. TC; OR=3.00, 95% CI: 1.56-5.75, P=0.009), and recessive model (CC vs. TC+TT; OR=3.00, 95% CI: 1.56-5.75, P=0.0008). For the NOS3 G894T (Glu298Asp) rs1799983 SNP, the multiplicative model showed a significant risk of TRH with the carriage of the T allele (OR=1.99, 95% CI: 1.20-3.28, P=0.007), and the additive model showed a significant risk of TRH with the carriage of the heterozygous GT genotype (OR=2.25, 95% CI: 1.17-4.33, P=0.01). At the same time, the carriage of the G allele (OR=0.5, 95% CI: 0.30-0.83, P=0.007) and GG genotype (OR=0.40, 95% CI: 0.21-0.76, P=0.01) may be protective against the development of TRH. Conclusion: Further genetic studies of TRH may help achieve better individual outcomes by optimizing drug therapy based on genetic variation.