Key result
The presence of 521T/T in the AGT gene, 1666C/C in the AGT2R1 gene, and -786C/C in the NOS3 gene was associated with increased endothelin-1 production, shifting the balance toward vasoconstriction.
Why the study?
To identify associations between allelic variants of AGT, AGT2R1, and NOS3 genes with endothelin-1 and nitric oxide production in young residents of the Russian North without cardiovascular disease.
Cross-Sectional (n=286)
No
Specific genetic polymorphisms in the AGT, AGT2R1, and NOS3 genes are associated with increased endothelin-1 levels and a shift towards vasoconstriction in healthy young adults in the Russian North.
The aim of the study was to identify associations between allelic variants of AGT, AGT2R1 and NOS3 genes with production of endo-thelin-1 (ET-1) and nitric oxide (NO) in young residents of the Russian North without a history of cardiovascular diseases. Methods. The sample consisted of 286 young adults (116 females and 170 males) born in the Arkhangelsk region. Single nucleotide polymorphisms in the AGT, AGT2R1 and NOS3 genes were determined by polymerase chain reaction (PCR). Plasma NO oxide and ET-1 levels were measured. Results. T704C polymorphism in AGT gene was not associated with the studied vasoactive endothelial factors. However, vasoactive factors production in homozygotes with mutant T/T alleles of C521T polymorphism in the same gene is shifted towards vasoconstrictive factors. The level of ET-1 in the group with T/T genotype was higher than in the groups with C/T and C/C genotypes (p = 0.006 and p = 0.04, respectively). Homozygotes with mutant C alleles of AGT2R1 gene had higher concentration of ET-1 as compared to homozygotes with wild-type A alleles (p = 0.012). Young men with 786 C/C of NOS3 gene had higher plasma concentration of ET-1 than individuals with C/T (p = 0.01) and T/T (p = 0.07). ET-1 was higher in the group of girls homozygotes with mutant C alleles, however no statistically significant differences were found. Conclusions. Our results suggest that the risk of imbalance in vasoactive factors in young healthy residents of the Russian North is associated with the increase in ET-1 production level, but not with NO level. The presence of 521 T/T genotype in AGT gene, 1666C/C in AGT2R1 gene and -786C/C in NOS3 gene increases the risk of vasoactive factors imbalance development towards vasoconstriction.
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Bebyakova et al. (2020) conducted a cross-sectional in Healthy (no cardiovascular diseases) (n=286). Polymorphisms in AGT (C521T), AGT2R1 (A1666C), and NOS3 (-786T>C) genes vs. Wild-type genotypes was evaluated on Plasma levels of endothelin-1 (ET-1) and nitric oxide (NO). The presence of 521T/T in the AGT gene, 1666C/C in the AGT2R1 gene, and -786C/C in the NOS3 gene was associated with increased endothelin-1 production, shifting the balance toward vasoconstriction.
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