POLYMORPHISM OF THE VITAMIN D RECEPTOR GENE AND ECHOCARDIOGRAPHY INDICATORS IN PATIENTS WITH CARDIOVASCULAR DISEASES
Abstract
The aim of the study was to compare the structural and functional parameters of the myocardium in different genotypes of polymorphic markers BsmI (B/b) (rs1544410) and FokI (F/f) (rs2228570) of the vitamin D receptor gene (VDR) in individuals with cardiovascular diseases (CVD). Materials and Methods. We examined 198 patients with CVD. BsmI and FokI of the VDR gene were determined by the polymerase chain reaction. The blood levels of parathyroid hormone, 25(OH)D total, endothelin-1, plasma renin activity were revealed by the method of enzyme immunoassay. The calcium and phosphorus level in the blood was defined by the colorimetric method. Echocardiography was performed by GE Logic P5 Premium (Korea) with a phased sector sensor with a frequency of 2–4 MHz in the modes M-, B-, PW, CW. Results. All participants were divided into groups according to genotypes of FokI and BsmI of the VDR gene. For each polymorphism, the groups were comparable in age, CVD, blood pressure, heart rate, body mass index and levels of the estimated biomarkers. Significant differences (p < 0.05) in the sizes of the aorta and the left atrium (LA), in the sizes and volumes of the left ventricle (LV) and its walls, the diameter of the LV outlet tract and the ejection fraction between the groups with the genotypes of FF and ff were established. In addition, differences (p < 0.05) were found in the aorta size, LA and interventricular septum between the groups with the genotypes of ff and Ff. According to the genotypes of BsmI of the VDR gene, the groups did not differ significantly in the estimated structural and functional parameters of the myocardium and aorta. Hypertrophy of the LV is diagnosed in 78.6 % of participants. Conclusions. Polymorphism of FokI, but not of BsmI of the VDR gene is associated with structural and functional parameters of the myocardium and aorta in individuals with CVD in the Grodno region of Belarus. With the greatest frequency, LV hypertrophy occurs with Ff (37.9 %) and Bb (33.8 %).
About the Authors
Victor A. SnezhitskiyBelarus
Corresponding Member, D. Sc. (Medicine), Professor, Rector
Gorkii Str., 80, 230009
Ludmila V. Yankouskaya
Belarus
Ph. D. (Medicine), Assistant Professor, Head of the Department
Gorkii Str., 80, 230009
Tatiana L. Stepuro
Belarus
Ph. D. (Biology), Researcher
Gorkii Str., 80, 230009
Victor I. Novogran
Belarus
Head of the Department
59, Leninskogo Komsomola Blvd., 230030
References
1. Mithal A., Wahl D. A., Bonjour J. P., Burckhardt P., Dawson-Hughes B., Eisman J. A., El-Hajj Fuleihan G., Josse R. G., Lips P., Morales-Torres J. IOF Committee of Scientific Advisors (CSA) Nutrition Working Group. Global vitamin D status and determinants of hypovitaminosis D. Osteoporosis International, 2009, vol. 20, no. 11, pp. 1807–1820. doi.org/10.1007/s00198- 009-0954-6
2. Yankouskaya L. V., Snezhitskiy V. A., Povoroznyuk V. V., Moiseenok A. G., Yahorchanka N. P. The relationship of vitamin D with age, sex, diagnosis and the factors of cardiovascular risk. Meditsinskii zhurnal = Medical Journal, 2017, no. 2, pp. 115–120 (in Russian).
3. Martins D., Wolf M., Pan D., Zadshir A., Tareen N., Thadhani R., Felsenfeld A., Levine B., Mehrotra R., Norris K. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Archives of Internal Medicine, 2007, vol. 167, no. 11, pp. 1159–1165. doi.org/10.1001/archinte.167.11.1159
4. Kendrick J., Targher G., Smits G., Chonchol M. 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the Third National Health and Nutrition Examination Survey. Atherosclerosis, 2009, vol. 205, no. 1, pp. 255–260. doi.org/10.1016/j.atherosclerosis.2008.10.033
5. Gupta G. K., Agrawal T., DelCore M. G., Mohiuddin S. M., Agrawal D. K. Vitamin D deficiency induces cardiac hypertrophy and inflammation in epicardial adipose tissue in hypercholesterolemic swine. Experimental and Molecular Pathology, 2012, vol. 93, no. 1, pp. 82–90. doi.org/10.1016/j.yexmp.2012.04.006
6. Tishkoff D. X., Nibbelink K. A., Holmberg K. H., Dandu L., Simpson R. U. Functional vitamin D receptor (VDR) in the t-tubules of cardiac myocytes: VDR knockout cardiomyocyte contractility. Endocrinology, 2008, vol. 149, no. 2, pp. 558– 564. doi.org/10.1210/en.2007-0805
7. Povoroznyuk V. V., Snezhitskiy V. A., Yankouskaya L. V., Maylyan E. A., Reznichenko N. A., Maylyan D. E. Extraskeletal effects of vitamin D: role in the pathogenesis of cardiovascular diseases. Zhurnal Grodnenskogo gosudarstvennogo meditsinskogo universiteta = Journal of the Grodno State Medical University, 2015, no. 2, pp. 6–14 (in Russian).
8. O’Connell T. D., Berry J. E., Jarvis A. K., Somerman M. J., Simpson R. U. 1,25-Dihydroxyvitamin D3 regulation of cardiac myocyte proliferation and hypertrophy. American Journal of Physiology – Heart and Circulatory Physiology, 1997, vol. 272, no. 4, pp. 1751–1758.
9. Norman P. E., Powell J. T. Vitamin D and Cardiovascular Disease. Circulation Research, 2014, vol. 114, no. 2, pp. 379–393. doi.org/10.1161/circresaha.113.301241
10. Mancia G., Fagard R., Narkiewicz K., Redon J., Zanchetti A., Böhm M., Christiaens T., Cifkova R., De Backer G., Dominiczak A., Galderisi M., Grobbee D. E., Jaarsma T., Kirchhof P., Kjeldsen S. E., Laurent S., Manolis A. J., Nilsson P. M., Ruilope L. M., Schmieder R. E., Sirnes P. A., Sleight P., Viigimaa M., Waeber B., Zannad F. ESH/ESC Guidelines for the management of arterial hypertension. Journal of Hypertension, 2013, vol. 31, no. 7, pp. 1281–1357. doi.org/10.1097/01. hjh.0000431740.32696.cc
11. Testa A., Mallamaci F., Benedetto F., Pisano A., Tripepi G., Malatino L., Thadhani R., Zoccali C. Vitamin D Receptor (VDR) Gene Polymorphism Is Associated With Left Ventricular (LV) Mass and Predicts Left Ventricular Hypertrophy (LVH) Progression in End-Stage Renal Disease (ESRD) Patients. Journal of Bone and Mineral Research, 2010, vol. 25, no. 2, pp. 313–319. https://doi.org/10.1359/jbmr.090717
12. El-Shehaby A. M., El-Khatib M. M., Marzouk S., Battah A. A. Relationship of BsmI polymorphism of vitamin D receptor gene with left ventricular hypertrophy and atherosclerosis in hemodialysis patients. Scandinavian Journal of Clinical and Laboratory Investigation, 2013, vol. 73, no. 1, pp. 75–81. doi.org/10.3109/00365513.2012.743163
13. Santoro D., Gagliostro G., Alibrandi A., Ientile R., Bellinghieri G., Savica V., Buemi M., Caccamo D. Vitamin D Receptor Gene Polymorphism and Left Ventricular Hypertrophy in Chronic Kidney Disease. Nutrients, 2014, vol. 6, no. 3, pp. 1029–1037. doi.org/10.3390/nu6031029
14. Schmidt S., Chudek J., Karkoszka H., Heemann U., Reichel H., Rambausek M., Kokot F., Ritz E. The BsmI vitamin D-receptor polymorphism and secondary hyperparathyroidism. Nephrology Dialysis Transplantation, 1997, vol. 12, no. 8, pp. 1 771–1772. doi.org/10.1093/oxfordjournals.ndt.a027783
15. Vigo Gago E., Cadarso-Suárez C., Perez-Fernandez R., Romero Burgos R., Devesa Mugica J., Segura Iglesias C. Association between vitamin D receptor FokI. Polymorphism and serum parathyroid hormone level in patients with chronic renal failure. Journal of Endocrinological Investigation, 2005, vol. 28, no. 4, pp. 117–121. doi.org/10.1007/bf03345353