Genetic features of heart remodeling in patients with diabetic nephropathy

Authors

  • A. Nesen L.T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine, Kharkiv, Ukraine
  • K. Savicheva L.T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine, Kharkiv, Ukraine
  • P. Semenovykh L.T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine, Kharkiv, Ukraine
  • T. Shcherban L.T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine, Kharkiv, Ukraine
  • I. Topchii L.T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine, Kharkiv, Ukraine

DOI:

https://doi.org/10.22141/2224-1485.15.1.2022.339

Keywords:

diabetes mellitus, diabetic nephropathy, ACE gene polymorphism, left ventricular hypertrophy

Abstract

Background. Diabetes mellitus (DM) is one of the highest priority medical and social problems today. The main causes of death in patients with diabetes are coronary heart disease, hypertension with the development of left ventricular (LV) myocardial hypertrophy and diabetic kidney disease. The aim of the study to determine the prevalence of the Alu Ins/Del polymorphism of the angiotensin-converting enzyme (ACE) gene in patients with type 2 DM with nephropathy and to identify a possible association between cardiac remodeling with genetic profile. Materials and methods. 73 patients with diabetic nephropathy (DN) were examined. The control group consisted of 19 healthy individuals. Depending on the polymorphic variant of the ACE gene, patients with type 2 DM were divided into three groups: group I — patients with DN and D/D polymorphism of the ACE gene (n = 23); group II — patients with DN and I/D polymorphism of the ACE gene (n = 32); Group III — patients with DN and I/I polymorphism of the ACE gene (n = 18). DNA amplification and genotyping were carried out by real-time polymerase chain reaction (PCR) using the SNP-EXPRESS-SHOT reagent kit (Litech, RF). All patients were diagnosed by transthoracic echocardiography on an ultrasound machine “ULTIMA PA” (“Radmir”, Ukraine) according to the recommendations of the American Echocardiographic Society. Results. In patients with the D/D genotype, the size of the left ventricle of the heart, as well as LV mass index (MI) is significantly higher than in I/D heterozygotes (p < 0.05). Significantly higher aortic ostium diameter observed in patients with I/I polymorphism than in homozygous variant of the D/D ACE gene carriers (p < 0.05). In patients with type 2 DM, homozygotes for the ACE D/D allele, there is a significant predominance of concentric hypertrophy in the structure of changes in LV geometry (78,3 %), compared with I/D heterozygotes (56,3 %) and I/I carriers polymorphism (66,7 %). We found a negative correlation between very-low-density lipoprotein (VLDL) cholesterol and LV ejective fraction and positive correlation with urinary creatinine concentration. The level of LDL-cholesterol was positively correlated with interventricular septal thickness (IVST) and posterior wall thickness (PWT) LV. There was also a positive correlation between urinary creatinine and LV volume. In patients with DN I/D polymorphism is associated with a reduced risk of LV mass over 251 g (OR = 0,24 (0,08–0,76); p = 0.012 — codominant model of inheritance; OR = 0,24 (0,09–0,63); p = 0,003 — overdominant model of inheritance). Conclusions. The heterozygous I/D genotype of the ACE gene is associated with a reduced risk of LV mass and LVMI growth compared to the D/D genotype, which indicates an important effect of this polymorphism not only on the pathogenesis of DN but also on the development and progression of cardiovascular disease in 2 type DM patients.

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Published

2022-07-01

How to Cite

Nesen, A., Savicheva, K., Semenovykh, P., Shcherban, T., & Topchii, I. (2022). Genetic features of heart remodeling in patients with diabetic nephropathy. HYPERTENSION, 15(1), 16–21. https://doi.org/10.22141/2224-1485.15.1.2022.339

Issue

Section

Clinical Researches