Vascular control parameters and gene polymorphism associated with cardiovascular risk in young and relatively healthy individuals

Aim. To study the relationship of polymorphism of APOC3, PON1, AGT, AGTR1 genes and Vascular control parameters (blood pressure — BP and heart rate — HR) when performing an orthostatic test in young individuals.

Material and methods. The study involved 75 relatively healthy Caucasian volunteers aged 20-25 years. The exclusion criterion was the presence of cardiovascular and central nervous pathologies. Vascular control was assessed by conducting an active orthostatic test. Identification of gene polymorphism was carried out by the method of deoxyribonucleic acid pyrosequencing.

Results. Persons with the presence of the risk C allele of the A1666C A>C polymorphism of the AGTR1 gene have a lower heart rate in the prone position. The pulse pressure (PP) of these persons in the first minute after the rise remained at higher values. The highest levels of PP in the first minute as well as heart rate were observed in individuals whose genotype simultaneously contains the risk allele of the A1666C A>C polymorphism of the AGTR1 gene and T207M C>T polymorphism of the AGT gene. After 1 min of orthostasis in individuals carrying the mutant allele of the A1666C A>C polymorphism of the AGTR1 gene diastolic blood pressure (DBP) increased lesser, and the pulse pressure decreased “weaker” in relation to the initial values. The presence of the M268T T>C polymorphism of the AGT gene in the genotype was associated with a less high systolic blood pressure (SBP) at the first minute of orthostasis, as well as a less significant increase in DBP. Persons whose genotype contains the T allele of the L55M A>T polymorphism of the PON1 gene had a lower SBD and PP in the prone position. The presence in the genotype of the T allele of the -482 C>T polymorphism of the APOC3 gene is associated with lower rates of DBP in the prone position and SBP on the first minute after the rise. Also these individuals showed a more pronounced heart rate increase after the rise.

Conclusion. There is a significant relationship between the studied polymorphic variants of the APOC3, PON1, AGT, AGTR1 genes and vascular control parameters in the context of orthostasis. It may be a predictor of early development of arterial hypertension.

1. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018;39(33):3021-104. doi:101093/eurheartj/ehy339.

2. Martynovich, TV, Akimova NS, Fedotov EA, et al. Gene polymorphism in association with atherosclerosis development and cognition disorders in patients with ischemic chronic heart failure. Cardiovascular Therapy and Prevention. 2015; 14(1 ):30-4. (In Russ.) doi:10.15829/1728-8800-2015-1 -30-34.

3. Martynovich TV, Akimova NS, Fedotov EA, et al. Analysis of the polymorphism of the genes of the renin-angiotensin-aldosterone system in patients with cardiovascular 9. diseases. Modern problems of science and education. 2015;3. http://www.science-education.ru/ru/article/view?id=17392 (11.02.2019). (In Russ.) http://www.science-education.ru/ru/article/view?id=17392 (11 февраля 2019).

4. Shvarts YG, Elkina AY, Akimova NS, et al. The genes associated with lipid metabolism disordes and with blood pressure regulation, and psychovegetative changes in the young almost healthy persons. Cardiovascular Therapy and Prevention. 2016;15(6):53-7. (In Russ.) doi:10.15829/1728-8800-2016-6-53-57.

5. Vejn AM. Vegetative disorders: clinic, diagnosis, treatment. M.: Med. inform. agentstvo, 2003. р. 752. (In Russ.) ISBN: 5-89481-066-3.

6. Olivieri O, Martinelli N, Girelli G, et al. Apolipoprotein C III predicts cardiovascular mortality in severe coronary artery disease and is associated with an enhanced thrombin generation. J Thromb Haemost. 2010;8:463-71. doi: 10.1111/j.1538-7836.2009.03720.x.

7. Kurdjukov ID. Paraoxonase-1: genetic, biochemical and toxicological aspects. Toxicological Review. 2011;1:48-55. (In Russ.)

8. Yap RWK, Shidoji Y, Yap WS, et al. Association and Interaction Effect of AGTR1 and AGTR2 Gene Polymorphisms with Dietary Pattern on Metabolic Risk Factors of Cardiovascular Disease in Malaysian Adults. Nutrients. 2017;9:E853. doi: 10.3390/nu9080853.

9. Kohli S, Kumar R, Gupta M, et al. Impact of interactions between risk alleles on clinical endpoints in hypertension. Heart Asia. 2016;8(1 ):83-9. doi: 10.1136/heartasia-2016-010723.

10. Karimov RN, Shvarts YG. Statistics for doctors in an understandable presentation. Saratov: Izdatel'stvo Saratovskogo medicinskogo universiteta, 2014. р. 60. (In Russ.) ISBN 978-5-7213-0526-9.

11. Samosyuk NI, Samosyuk IZ, Chukhraeva EN, et al. Some structural and functional features of the autonomic nervous system and their diagnosis in clinical practice in the treatment and rehabilitation of patients of various profiles with autonomic disorders. Journal of Education, Health and Sport. 2015;5(3):103-65. (In Russ.) doi: 10.5281/zenodo.16256.