Vol. 28 No. 4 (2024)
PATHOPHYSIOLOGY

Gene variability of natriuretic peptides in patients with rheumatic heart disease and atrial fibrillation

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  • A.V. Sinitskaya,
  • M.V. Khutornaya,
  • O.N. Hryachkova,
  • A.O. Poddubnyak,
  • M.A. Asanov,
  • M.Yu. Sinitsky
A.V. Sinitskaya
Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo
Bio
M.V. Khutornaya
Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo
O.N. Hryachkova
Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo
A.O. Poddubnyak
Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo
M.A. Asanov
Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo
M.Yu. Sinitsky
Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo
Central illustration
DOI: https://doi.org/10.21688/1681-3472-2024-4-59-67

Published 2024-12-27

Keywords

  • Atrial Fibrillation,
  • Gene Polymorphism,
  • Genotype,
  • Heart Valve Diseases,
  • Natriuretic Peptides,
  • Rheumatic Heart Disease
    • ...More
    Less

How to Cite

Sinitskaya, A., Khutornaya, M., Hryachkova, O., Poddubnyak, A., Asanov, M. ., & Sinitsky, M. (2024). Gene variability of natriuretic peptides in patients with rheumatic heart disease and atrial fibrillation. Patologiya Krovoobrashcheniya I Kardiokhirurgiya, 28(4), 59–67. https://doi.org/10.21688/1681-3472-2024-4-59-67

Copyright (c) 2024 Sinitskaya A.V., Khutornaya M.V., Hryachkova O.N., Poddubnyak A.O., Asanov M.A., Sinitsky M.Yu.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Introduction: Atrial fibrillation (AF) is one of the most common arrhythmias in rheumatic heart disease (RHD) patients. The pathophysiological mechanisms of AF development against the background of RHD are still understudied. Similarly to most cardiovascular pathologies, AF is a multifactorial disease with a significant genetic predeterminacy.
Objective: The study was aimed at searching for associations of polymorphic gene variants of the natriuretic peptides (NPPA, NPPB and NPPC) with the AF risk in RHD patients.
Methods: The study included 251 patients diagnosed with RHD, who were divided into 2 groups: patients with RHD and AF (n = 191) and patients with RHD without AF (n = 60). Genotyping of 7 allelic variants of genes encoding natriuretic peptides was performed using real-time polymerase chain reaction.
Results: Polymorphic variants rs198388 and rs198389 of the NPPB gene were found to have a protective effect against the AF in RHD patients on the model of a codominant inheritance. The rs198358 allelic variant of the NPPA-AS1 gene was associated with the two-fold increased AF risk in RHD patients (OR 1.96, 95% CI 1.02-3.75, p = 0.037). Two models of gene-gene interactions characterized by the high efficacy and sensitivity have been identified in this study. The most significant combinations of genotypes associated with an increased AF risk in RHD patients were rs198388 C/T × rs198389 A/G × rs198358 T/C × rs5063 C/C × rs632793 A/G and rs198388 C/T × rs198358 T/ C × rs5063 C/C.
Conclusion: Polymorphic gene variants of the natriuretic peptides (NPPB rs198388, rs198389 and NPPA-AS1 rs198358), associated with AF risk, were identified in RHD patients. Three-locus (NPPB rs198388, NPPA-AS1 rs198358 and NPPA rs5063) and five-locus (NPPB rs198388, NPPB rs198389, NPPA-AS1 rs198358, NPPA rs5063 and NPPA rs632793) models of gene-gene interactions were associated with the studied phenotype.

Received 16 April 2024. Revised 10 October 2024. Accepted 2 November 2024.

Funding
This research was supported by the Complex Program of Fundamental Research of the Siberian Branch of the Russian Academy of Sciences within the framework of the fundamental research project of the Research Institute for Complex Issues of Cardiovascular Diseases No. 0419-2022-0001.

Conflict of interest
The authors declare no conflict of interest.

Contribution of the authors
Conception and study design: A.V. Sinitskaya, M.V. Khutornaya
Data collection and analysis: O.N. Hryachkova, A.O. Poddubnyak, M.V. Khutornaya, M.A. Asanov
Statistical analysis: A.V. Sinitskaya
Drafting the article: A.V. Sinitskaya
Critical revision of the article: M.Yu. Sinitsky
Final approval of the version to be published: A.V. Sinitskaya, M.V. Khutornaya, O.N. Hryachkova, A.O. Poddubnyak, M.A. Asanov, M.Yu. Sinitsky

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