Interaction of oestradiol and vasoactive factors in women with rs 2070744 polymorphism of endothelial NO-synthase gene
https://doi.org/10.1234/YMJ.2022.77.02
Abstract
The aim of this study is the identification of interaction of oestradiol and vasoactive endothelial factors in women with polymorphism T-786C of endothelial nitric oxide synthase (eNOS) gene during follicular and luteal phase of the menstrual cycle. Sample size was 116 women with average age 19,6 years (95% CI 18,4 – 22,4), being born and living in the circumpolar region. Genotyping of T-786C polymorphism of eNOS gene was performed by pyrosequencing. The peripheral vascular tone was evaluated by tetrapolar reography. Concentration of nitric oxide (NO) was measured by Griss reaction. The level of oestradiol and endothelin-1 (ET-1) was measured by ELISA (enzyme-linked immunosorbent assay). Index ratio vasodilator to vasoconstrictor was calculated (NO/ET-1). «SPSS statistics» (StatSoft, USA) was used for statistical analyses. Our study found that the frequency of T allele was 0,67, C allele – 0,33 and C/C genotype was the rarest. The highest concentration of NO was found in women with C/C genotype during follicular phase. The concentration of NO in luteal phase in women with different genotypes of eNOS gene was similar. The level of ET-1 in women with T/T and C/T genotypes was normal during follicular and luteal phase, but in women with C/C genotype the level of ET-1 was above the normal reference range during follicular and luteal phase. The study of peripheral vascular tone found that C/C genotype was correlated with higher level of index of peripheral resistance (IPR) during follicular phase after dosed physical test, higher level of IPR was before and after dosed physical testduring luteal phase. The concentration of oestradiol in women with T/T and C/T genotypes was higher during luteal phase, in women with C/C genotype the level of oestradiol was higher in follicular phase. Correlation analysis between oestradiol and NO determined the moderate correlation (r=0,302; p=0,05) in C/T genotype, the strong positive association in C/C genotype during follicular phase (r=0,755, p=0,03) and luteal phase, and no association in T/T genotype. Thus, it was revealed that the presence of both mutant alleles C was correlated with imbalance of vasoactive factors (higher level of vasoconstrictors), leading to higher vascular peripheral tone. Also it was found that the association between oestradiol and NO manifested only in case of presence of mutant allele C of polymorphism T-786C gene of eNOS in genotype, that can approve protective function of oestradiol in relation to NO synthesis and can be confirmed by higher level of NO in women with C/C genotype during follicular phase of cycle.
About the Authors
N. A. Bebyakova
Northern Medical State University
Russian Federation
Russian Federation
Nataliya A. Bebyakova – Doctor of Biological Sciences, Professor, Head of the Department of Medical Biology and Genetics, Northern Medical State University.
Arkhangelsk
A. A. Kuba
Northern Medical State University
Russian Federation
Russian Federation
Anastasia A. Kuba – lecturer - researcher, Department of Medical Biology and Genetics, Northern Medical State University.
Arkhangelsk
N. A. Fadeeva
Northern Medical State University
Russian Federation
Russian Federation
Nataliya A. Fadeeva – lecturer - researcher, Department of Medical Biology and Genetics, Northern Medical State University.
Arkhangelsk
A. V. Khromova
Northern Medical State University
Russian Federation
Russian Federation
Anna V. Khromova – Candidate of Medical Sciences, Associate Professor, Dean of the Faculty of Preventive Medicine and Medical Biochemistry, Northern Medical State University.
Arkhangelsk
References
1. Bebyakova N.A. Polymorphism of genes AGT, AGT2R1 and NOS3 as a risk factor for the development of imbalance of vasoactive factors [Structural and functional properties of vascular endothelium] / N.A. Bebyakova, O.A. Pervukhina, N.A. Fadeeva, A.V. Khromova // Human Ecology. - 2020. -No. 10. - S. 4-9.
2. Vardugina N.G. Cardiovascular risk stratification in women with early oestrogen deficiency] / N.G. Vardugina, T.A. Azarenkova // Russian Journal of Cardiology. - 2010. -Vol. 84 (4). -P. 24-28.
3. Gerilovich L.A. Clinical role of predictors of angiogenesis and endothelial dysfunction in outcomes prediction of assisited reproductive technologies program: 14.01.01.Cand.sci.Dissertation. – Krasnoyarsk State Medical University. - 2015. -P. 112.
4. Zhad'ko D.D. Polymorphism of endothelial nitric oxide synthase. Part 1. G894C gene polymorphism (GLU298ASP, RS1799983)] / D.D. Zhad'ko, V.V. Zinchuk// Journal of the Grodno State Medical University. 2017. № 1. - P 5-12.
5. Kade A. H. Physiological functions of vascular endothelium / A. H. Kade, S.A. Zanin, E.A. Gubareva // Fundamental research. - 2011. - №11(p. 3). - P. 611-617.
6. Kuznetsov I.V. Endothelial Dysfunction as a Link Between Climacteric Syndrome and Cardiovascular Diseases] / I.V. Kuznetsov // Effective pharmacotherapy. - 2019. - Vol.15, № 32. - P.32-40.
7. Komzin K.V. Polymorphisms of genes involved in blood pressure regulation in different ethnic groups of residents of Far North of Yakutia with arterial hypertension / K.V. Komzin // Bulletin of North-Eastern Federal University. Part: Medical science. - 2019. -№4(17). - P.5-12.
8. Pahomya N.S. Role of some gene polymorphisms in arterial hypertension / N.S. Pahomya, O.M. Uryasyev, A.V. Shahanov // Zemskiy vrach. - 2014.- № 3–4 (24). - P. 21-24.
9. Chakrabarti S., Davidge S.T. G-Protein Coupled Receptor 30 (GPR30): A Novel Regulator of Endothelial Inammation // PLoS ONE. 2012. Vol. 7 (12). E. 52357.
10. Duckles S.P., Miller V.M. Hormonal modulation of endothelial NO production. // Pflügers Arch. Eur. J. Physiol. 2010 V.459(6). P.841–851.
11. GreenD.J., MaioranaA., O`DriscolG. L., TaylorR. Effect of exercisetra in ingonen do the lium-derived nitric oxide function in humans // Journal of Physiology. 2004. Vol. 561 (Pt. 1). P. 1–25
12. Kim K.H., Bender J.R. Membrane-initiated actions of estrogen on the endothelium. // Mol. Cell. Endocrinol. 2009. V.308(1-2). P.3–8.
13. Kypreos K.E., Zarovic S., Petropoulou P.-I. et al. Regulation of endothelial nitric oxide synthase and high-density lipoprotein quality by estradiol in cardiovascular pathology // Journal of Cardiovascular Pharmacology and Therapeutics. 2014. Vol. 19. P. 256–2
14. MacRitchie A.N., Jun S. S., Chen Z. et al. Estrogen upregulates endotheial nitric oxide synthase gene expression in fetal pulmonary artery endothelium // Circ. Res. 1997. Vol. 81. P. 355–362.
15. Miyamoto Y., Saito Y. et al. Replication protein A1 reduces transcription of the endothelial nitric oxide synthase gene containing a -786T—>C mutation associated with coronary spastic angina // Hum Mol Genet. 2000. Vol. 9 (18). P. 2629–2637
16. Siow R.C. M., Li F.Y., Rowlands D.J., de Winter P., Mann G.E. Cardiovascular targets for estrogens and phytoestrogens: transcriptional regulation of nitric oxide synthase and antioxidant defense genes. // Free Radic. Biol. Med. 2007. V.42(7). P.909–925.
17. Yaghoubi AR, Khaki-Khatibi F. t-786C single-nucleotide polymorphism (sNP) of endothelial nitric oxide synthase gene and serum level of vascular endothelial relaxant factor (VeRF) in nondiabetic patients with coronary artery disease. African Journal of Biotechnology. 2012. 11 (93). Р.15945-9.
Review
For citations:
Bebyakova N.A., Kuba A.A., Fadeeva N.A., Khromova A.V. Interaction of oestradiol and vasoactive factors in women with rs 2070744 polymorphism of endothelial NO-synthase gene. Yakut Medical Journal. 2022;(1):8-10. https://doi.org/10.1234/YMJ.2022.77.02
Views:
20
Email this article 