CORRELATION OF GENETIC POLYMORPHISM OF CALCIUM ION CHANNELS RYR2, CACNA1H, CACNA1C WITH THE DEVELOPMENT OF LEFT VENTRICULAR MYOCARDIAL HYPETROPHY IN PATIENTS WITH ESSENTIAL HYPERTENSION

Aim. The correlation of genetic polymorphism of calcium-ion channels RYR2, CACNA1H, CACNA1C with the development of left ventricular myocardial hypertrophy in patients with essential hypertension was studied.

Methods. The study was performed in 84 patients with essential arterial hypertension with myocardial hypertrophy confirmed by echocardiography, and 80 patients with essential hypertension without myocardial hypertrophy. The detection of the SNP of calcium channel RYR2 (rs2490389), CACNA1H (rs11865472), CACNA1C (rs1006737), CACNA1 (rs11079919) genes was carried out by PCR by real-time PCR. Genotype frequencies were verified to concordance of Hardy-Weinberg equilibrium. The χ2-test were done, and the odds ratio (OR) are estimated.

Results. It was established that the frequency of the minor allele and the TT genotype of SNP G237115840T (rs2490389) of the RYR2 gene in patients with essential hypertension with myocardial hypertrophy is higher than in patients with essential hypertension without hypertrophy. The risk of the left ventricular myocardial hypertrophy development in patients with essential hypertension was higher in carriers of the T allele (OR=2,10[95% СI: 1,34 – 3,27], р<0,001) and the TT genotype (OR=2,85 [95% СI: 1,44 – 5,61], р<0,01) SNP G237115840T (rs2490389) SNP G237115840T (rs2490389) of the RYR2 gene.

The G allele and the GG genotype of the G2236129A polymorphism of the CACNA1H gene (rs11865472) were more common in the group of patients with essential hypertension and the left ventricular myocardial hypertrophy. The risk of developing myocardial hypertrophy in patients with essential arterial hypertension was higher in carriers of the G allele (OR=2,06[95% СI: 1,33 – 3,20], р<0,001) and the GG genotype (OR=2,86 [95% СI: 1,36 – 6,02], р<0,01) SNP G1134967A (rs11865472) of the CACNA1H gene of the potentially-gated calcium channel molecule. At the same time, the frequency of the minor allele SNP G2236129A (rs1006737) of the CACNA1C gene is not differ from each other.

Conclusions. Carrying the T allele and the TT genotype SNP G237115840T (rs2490389) of the RYR2 gene, the G allele and the GG genotype SNP G1134967A (rs11865472) of the CACNA1H gene are risks for development of the left ventricular myocardial hypertrophy in patients with essential arterial hypertension.

1. Pushkarev B.S. The role of genetic polymorphism of calcium ion channels in the pathogenesis of essential hypertension [dissertation]. Chita. Chita state medical academy. 2020. in Russian.

2. Pushkarev B.S., Vitkovsky Y.A. Calcium ion channels. Part I. Transbaikal medical journal. 2015. 4. 175–182. [cited 15.04.2022]. Available from: http://zabmedvestnik.ru/journal/2015/4/31.pdf.

3. Pushkarev B.S., Vitkovsky Y.A. Calcium ion channels. Part II. Transbaikal medical journal. 2016. 1. 93–104. [cited 15.04.2022]. Available from: http://zabmedvestnik.ru/journal/2016/1/15.pdf.

4. Gong S., Bin Su B., Tovar H., Mao C., Gonzalez V., Liu Y., Lu Y., Wang K., Xu C. Polymorphisms within RYR3 gene are associated with risk and age at onset of hypertension, diabetes, and Alzheimer's disease. 2018 Jun 11. 31(7). 818-826. DOI:10.1093/ajh/hpy046.

5. Pushkarev B.S., Tereshkov P.P., Vitkovsky Yu.A. The influence of genetic polymorphism of calcium ion channels on the intracellular concentration of calcium ions both in healthy people and patients with hypertension. Transbaikal medical journal. 2019. 3. 158–168. [cited 20.03.2022]. in Russian. Available from: http://zabmedvestnik.ru/journal/2019/3/8.pdf.

6. Zhang H., Zhou J., Mu Y., Shrestha S., Wang N., Jian B., Jin M., Zhang K., Cong M., Liu J., Qiu C., Pushkarev B., Bolshakova O., Vitkovsky Y. CACNA1C (rs1006737) SNP increases the risk of essential hypertension in both Chinese Han and ethnic Russian people of Northeast Asia. Medicine (Baltimore). 2021. 10(8). e24825. DOI: 10.1097/MD.0000000000024825. – EDN MHNFII.

7. Zhang L., Sun Y., Zhang X., Shan X., Li J., Yao Y., Shu Y., Lin K., Huang X., Yang Z., Chu J., Huang L., Sun H. Three novel genetic variants in the FAM110D, CACNA1A, and NLRP12 genes are associated with susceptibility to hypertension among Dai people. American journal of hypertension. 2021 Aug 9. 34(8). 874-879. DOI: 10.1093/ajh/hpab040.

8. Kohli U., Kuntz L., Nayak H. RYR2 p.R169L mutation and left ventricular hypertrophy in a child with emotion-triggered sudden death. Cardiology in the Young. 2020 Jun 9. 30(7). 1039-1042. DOI: 10.1017/S1047951120001316.

9. World Medical Organization. Declaration of Helsinki. British Medical Journal. 1996 Dec 7. 313(7070). 1448-1449. (File revised 1998 Dec 20, 2000 June 7). [cited 20.03.2022]. Available from: http://www.cirp.org/library/ethics/helsinki.

10. Visseren F.L.J., et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC). European Heart Journal. 2021. 42 (34). 3227–3337. DOI.org/10.1093/eurheartj/ehab484.

11. Williams B., Mancia G., Spiering W., Agabiti Rosei E., Azizi M., Burnier M., Clement D.L., Coca A., de Simone G., Dominiczak A., Kahan T., Mahfoud F., Redon J., Ruilope L., Zanchetti A., Kerins M., Kjeldsen S.E., Kreutz R, Laurent S, Lip GYH., McManus R., Narkiewicz K., Ruschitzka F., Schmieder R.E., Shlyakhto E., Tsioufis C., Aboyans V., Desormais I; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018. 39 (33). 3021–3104. DOI: 10.5603/KP.2019.0018.

12. Ganau A., Devereux R.B., Roman M.J., de Simone G., Pickering T.G., Saba P.S., Vargiu P., Simongini I., Laragh J.H. Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension. J. Am. Coll. Cardiol. 1992 Jun. 19(7). 1550-8. DOI: 10.1016/0735-1097(92)90617-v.