Association of β1-, β2-Adrenoceptor and LGALS-3 Genes Polymorphisms with the Course of Heart Failure in Patients with Ischemic Heart Disease

DOI: https://doi.org/10.30702/ujcvs/24.32(02)/K039-2232
Keywords: risk, rehospitalization, atrial fibrillation, diabetes mellitus, postinfarction cardiosclerosis, mutation

Abstract

The aim. To study the relationship between β1-, β2-adrenoceptor (β-AR) and LGALS-3 genes polymorphisms with the course of heart failure (HF) in patients with coronary heart disease.

Materials and methods. We examined 201 patients with HF on the background of post-infarction cardiosclerosis. Control group included 43 healthy individuals of comparable age and sex. Genotyping was carried out for 4 polymorphisms (rs1801253 and rs1801252 of the β1-AR gene; rs1042714 of the β2-AR gene and rs2274273 of the LGALS-3 gene). Statistical analysis was performed using Statistica 10.0 and SNPStats programs.

Results. In patients with HF, the A allele (A/G-A/A) of the rs1801252 polymorphism of the β1-AR was associated with a reduced risk of rehospitalization (RH) within a year (odds ratio [OR] = 0.44 [0.20-0 .98], p = 0.036, dominant inheritance model). The data on the reduction of the risk of RH in patients with HF in the presence of the A allele of the rs1801252 polymorphism of the β1-AR gene were also confirmed in the log-additive (OR = 0.44 [0.20-0.96], p = 0.027) and, mainly, in excessively dominant (OR = 0.48 [0.21-1.06], p = 0.059) inheritance models. The analysis showed a higher frequency of allele A of the rs1801252 polymorphism of the β1-AR gene in the group of patients with HF who did not have RH due to decompensation during the year, compared to patients with RH (14.9% versus 7.0%, respectively; χ2 = 4.304; p = 0.039). The A allele of the specified gene polymorphism was also associated with a reduced risk of persistent atrial fibrillation (AF) (OR = 0.34 [0.14-0.84], p = 0.018, dominant inheritance model). This regularity was confirmed in the overdominant (OR = 0.27 [0.11-0.69], p = 0.0048) and in the codominant (OR = 0.28 [0.11-0.72], p = 0.0081) inheritance models. The A allele (A/G-A/A) of the rs2274273 polymorphism of the LGALS-3 gene was associated with an increased risk of AF in patients with HF (OR = 6.63 [1.31-33.53], p = 0.032, codominant inheritance model). Data on the increase in the risk of AF, provided that the A allele of the aforementioned polymorphism is present, were also confirmed in the recessive (OR = 5.12 [1.08-24.24], p = 0.017) and log-additive (OR = 2.11 [1.13-3.94], p = 0.015) inheritance models. The risk of RH in patients with HF and concomitant diabetes mellitus increased in patients with heterozygous (G/C) polymorphism rs1801253 of the β1-AR gene (OR = 3.91 [1.03-14.87], p = 0.0041).

Conclusions. The course of HF was associated with genetic differences β1-AR, in particular: the A allele of the rs1801252 polymorphism of the specified gene reduced the risk of RH within a year (14.1 % vs. 27.0 %; OR = 0.44; p = 0.036, dominant inheritance model) and AF (18.3 % vs. 39.5 %; OR = 0.34; p = 0.018, dominant inheritance model). The risk of RH of patients with HF and accompanying diabetes mellitus was higher with heterozygous (G/C) rs1801253 polymorphism of the β1-AR gene (24.4 % vs. 11.1 %; OR = 3.91; p = 0.0041). The A allele of the rs2274273 polymorphism of the LGALS-3 gene was associated with an increased risk of AF in patients with HF (20.0 % vs. 4.7%; OR = 6.63, p = 0.032, codominant inheritance model). No probable association of the rs1042714 polymorphism of the β2-AR gene with the course of HF was found.

References

  1. Boned BP, Marco LC, Callejas GI. [Dilated Cardiomyopathy: Presentation of a Clinical Case]. Arch Med Fam. 2023;25(2):103-106. Spanish.
  2. McDonagh TA, Metra M, Adamo M, Gardner RS,Baumbach A, Böhm M, et al.; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-3726. https://doi.org/10.1093/eurheartj/ehab368
  3. Levin MG, Tsao NL, Singhal P, Liu C, Vy HMT, Paranjpe I, et al. Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure. Nat Commun. 2022;13(1):6914. https://doi.org/10.1038/s41467-022-34216-6
  4. dbSNP Short Genetic Variations: 1801252 frequency. Available from: https://www.ncbi.nlm.nih.gov/snp/rs1801252#frequency_tab [cited September 21, 2022].
  5. Dorn GW 2nd, Liggett SB. Mechanisms of Pharmacogenomic Effects of Genetic Variation within the Cardiac Adrenergic Network in Heart Failure. Mol Pharmacol. 2009;76(3):466-480. https://doi.org/10.1124/mol.109.056572
  6. dbSNP Short Genetic Variations: 1801253 frequency. Available from: https://www.ncbi.nlm.nih.gov/snp/rs1801253#frequency_tab [cited September 21, 2022].
  7. Rathz DA, Gregory KN, Fang Y, Brown KM, Liggett SB. Hierarchy of Polymorphic Variation and Desensitization Permutations Relative to beta 1- and beta 2-Adrenergic Receptor Signaling. J Biol Chem. 2003;278(12):10784-10789. https://doi.org/10.1074/jbc.M206054200
  8. Levin MC, Marullo S, Muntaner O, Andersson B, Magnusson Y. The Myocardium-protective Gly-49 Variant of the beta 1-Adrenergic Receptor Exhibits Constitutive Activity and Increased Desensitization and Down-regulation. J Biol Chem. 2002;277(34):30429-30435. https://doi.org/10.1074/jbc.M200681200
  9. Metaxa S, Missouris C, Mavrogianni D, Miliou A, Oikonomou E, Toli E, et al. Polymorphism Gln27Glu of β2 Adrenergic Receptors in Patients with Ischaemic Cardiomyopathy. Curr Vasc Pharmacol. 2018;16(6):618-623. https://doi.org/10.2174/1570161115666170919180959
  10. dbSNP Short Genetic Variations: rs1042714 frequency [Internet]. Available from: https://www.ncbi.nlm.nih.gov/snp/rs1042714#frequency_tab [cited September 21, 2022].
  11. Covolo L, Gelatti U, Metra M, Nodari S, Piccichè A, Pezzali N, et al. Role of beta1- and beta2-adrenoceptor polymorphisms in heart failure: a case-control study. Eur Heart J. 2004;25(17):1534-1541. https://doi.org/10.1016/j.ehj.2004.06.015
  12. Mansur AJ, Fontes RS, Canzi RA, Nishimura R, Alencar AP, de Lima AC, et al. Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly in patients with heart failure. BMC Cardiovasc Disord. 2009;9:50. https://doi.org/10.1186/1471-2261-9-50
  13. Polishchuk TV, Zhebel VM. [Parameters of intra-cardiac hemodynamics in women with essential hypertension and heart failure, carriers of different polymorphic variants of the galectin-3 gene (LGALS-3, RS 2274273)]. Visnyk Vinnytskoho natsionalnoho medychnoho universytetu. 2023;27(2):258-263. Ukrainian. https://doi.org/10.31393/reports-vnmedical-2023-27(2)-13
  14. Hara A, Niwa M, Kanayama T, Noguchi K, Niwa A, Matsuo M, et al. Galectin-3: A Potential Prognostic and Diagnostic Marker for Heart Disease and Detection of Early Stage Pathology. Biomolecules. 2020;10(9):1277. https://doi.org/10.3390/biom10091277
  15. Soares LC, Al-Dalahmah O, Hillis J, Young CC, Asbed I, Sakaguchi M, et al. Novel Galectin-3 Roles in Neurogenesis, Inflammation and Neurological Diseases. Cells. 2021;10(11):3047. https://doi.org/10.3390/cells10113047
  16. Djordjevic A, Dekleva M, Zivkovic M, Stankovic A, Markovic Nikolic N, Alavantic D, et al. Left ventricular remodeling after the first myocardial infarction in association with LGALS-3 neighbouring variants rs2274273 and rs17128183 and its relative mRNA expression: a prospective study. Mol Biol Rep. 2018;45(6):2227-2236. https://doi.org/10.1007/s11033-018-4384-4
  17. Zhang Y, Wang Y, Zhai M, Gan T, Zhao X, Zhang R, et al. Influence of LGALS3 gene polymorphisms on susceptibility and prognosis of dilated cardiomyopathy in a Northern Han Chinese population. Gene. 2018;642:293-298. https://doi.org/10.1016/j.gene.2017.11.026
  18. Seferović PM, Jankowska E, Coats AJS, Maggioni AP, Lopatin Y, Milinković I, et al.; Task Force of the HFA Atlas, and the ESC Atlas of Cardiology leadership, developed in collaboration with the National Heart Failure Societies of the ESC member and ESC affiliated member countries. The Heart Failure Association Atlas: rationale, objectives, and methods. Eur J Heart Fail. 2020;22(4):638-645. https://doi.org/10.1002/ejhf.1768
  19. Graffelman J, Weir BS. The transitivity of the Hardy-Weinberg law. Forensic Sci Int Genet. 2022;58:102680. https://doi.org/10.1016/j.fsigen.2022.102680
  20. Amar J, Brunel J, Cardot Bauters C, Jacques V, Delmas C, Odou MF, et al. Genetic biomarkers of life-threatening pheochromocytoma-induced cardiomyopathy. Endocr Relat Cancer. 2022;29(5):267-272. https://doi.org/10.1530/ERC-21-0373
  21. Albuquerque FN, Brandão AA, Silva DA, Rocha RM, Bittencourt MI, Sales ALF, et al. Ser49Gly Beta1-Adrenergic Receptor Genetic Polymorphism as a Death Predictor in Brazilian Patients with Heart Failure.Arq Bras Cardiol. 2020;114(4):616-624. https://doi.org/10.36660/abc.20190187
  22. Pereira-Barretto AC. Short Editorial: Ser49Gly Beta1-adrenergic Receptor Genetic Polymorphism as a Death Predictor in Brazilian Patients with Heart Failure. Arq Bras Cardiol. 2020;114(4):625-626. https://doi.org/10.36660/abc.20200183
  23. Nascimento BC, Pereira SB, Ribeiro GS, Mesquita ET. Beta1-adrenergic Receptor Polymorphisms Associated with Atrial Fibrillation in Systolic Heart Failure. Arq Bras Cardiol. 2012;98(5):384-389. https://doi.org/10.1590/s0066-782x2012005000037
  24. Parvez B, Chopra N, Rowan S, Vaglio JC, Muhammad R, Roden DM, et al. A Common β1-Adrenergic Receptor Polymorphism Predicts Favorable Response to Rate-Control Therapy in Atrial Fibrillation. J Am Coll Cardiol. 2012;59(1):49-56. https://doi.org/10.1016/j.jacc.2011.08.061
  25. Fu H, Nie S, Luo P, Ruan Y, Zhang Z, Miao H, et al. Galectin-3 and acute heart failure: genetic polymorphisms, plasma level, myocardial fibrosis and 1-year outcomes. Biomark Med. 2020;14(11):943-954. https://doi.org/10.2217/bmm-2020-0269
Published
2024-06-27
How to Cite
Kulaiets, N. M. (2024). Association of β1-, β2-Adrenoceptor and LGALS-3 Genes Polymorphisms with the Course of Heart Failure in Patients with Ischemic Heart Disease. Ukrainian Journal of Cardiovascular Surgery, 32(2), 22-32. https://doi.org/10.30702/ujcvs/24.32(02)/K039-2232
Issue
Ukrainian Journal of Cardiovascular Surgery Vol 32 No 2 2024
Section
ISCHEMIC HEART DISEASE