Single nuclear polymorphism Val66Met (rs6265) of brain derived neurotrophic factor gene in prognostication of outcomes after ST segment elevation myocardial infarction
Article Sidebar
Main Article Content
Abstract
The aim – to investigate associations between single nucleotide polymorphism (SNP) Val66Met of the brain-derived neurotropic factor (BDNF) gene and conventional predictive biomarkers and combined 6-month clinical end points in post-ST segment elevation myocardial infarction (STEMI) patients.
Materials and methods. Two hundred and fifty six acute STEMI patients after successful percutaneous coronary intervention with TIMI III blood flow restoring. Single nuclear polymorphism Val66Met of BDNF gene was determined by real-time polymerase chain reaction. Observation behind the patients has been performed during 6-month period.
Results and discussion. The combined clinical end point (MACEs and hospitalization) after 6 month was determined in 61 (23.8 %) post-STEMI patients; 195 (7.2 %) patients did not meet the events. The frequency of Val66Met polymorphous genotypes of BDNF gene in STEMI patients was the following: Val66Val – 74.2 % (n=190), Val66Met + Met66Met – 25.8 % (n=66). Unadjusted multivariate linear regressions has shown that peak TnI levels, NT-proBNP, SYNTAX score, TIMI score, and Val66Met+Met66Met genotype of BDNF gene, remained independent predictors for combined clinical end point. After adjustment for SYNTAX score and TIMI score, genotype Val66Met+Met66Met of BDNF gene (OR 1.5476, 95 % CI 1.1277–4.1426, р=0.0246) and NT-proBNP (OR 1.7546, 95 % CI 1.0219–3.1002, р=0.046) were independent predictors for combined clinical end point. Kaplan – Meier curves demonstrated that post-STEMI patients having Val66Val genotype of BDNF gene had the lowest accumulation of combined end point when compared with those who had the combination of Va66lMet and Met66Met genotypes (Cox-criterion, p=0.019; log-rang criterion, p=0.03).
Сonclusions. The Val66Met polymorphism of BDNF gene was found as an independent predictor for combined 6-month clinical end points amid post-STEMI patients treated with percutaneous coronary intervention.
Article Details
Keywords:
References
Bahls M., Könemann S., Markus M.R.P. et al. Brain-derived neurotrophic factor is related with adverse cardiac remodeling and high NTproBNP // Sci Rep.– 2019.– Vol. 9 (1).– P. 15421. doi: https://doi.org/10.1038/s41598-019-51776-8.
Barman H.A., Şahin I., Atıcı A. et al. Prognostic significance of brain-derived neurotrophic factor levels in patients with heart failure and reduced left ventricular ejection fraction // Anatol. J. Cardiology.– 2019.– Vol. 22 (6).– P. 309–316. doi: https://doi.org/10.14744/AnatolJCardiol.2019.37941.
Berezin A.E. Circulating biomarkers in heart failure // Adv. Exp. Med. Biol.– 2018.– Vol. 1067.– P. 89–108. doi: https://doi.org/10.1007/5584_2017_140.
Cosentino F., Grant P.J., Aboyans V. et al., ESC Scientific Document Group, 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD) // Eur. Heart J.– 2020.– Vol. 41 (2).– P. 255–323. doi: https://doi.org/10.1093/eurheartj/ehz486
Costa H.S., Lima M.M.O., Figueiredo P.H.S. et al. Prognostic value of serum brain-derived neurotrophic factor levels in patients with Chagas cardiomyopathy // Mem. Inst. Oswaldo Cruz.– 2018.– Vol. 113.– P. e180224. doi: https://doi.org/10.1590/0074-02760180224.
Di Chiara A., Clagnan E., Valent F. Epidemiology and mortality in an Italian region after the adoption of the universal definition of myocardial infarction // J. Cardiovasc. Med. (Hagerstown).– 2020.– Vol. 21 (1).– P. 34–39. doi: https://doi.org/10.2459/JCM.0000000000000893.
Eagle K.A., Lim M.J., Dabbous O.H. et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month post-discharge death in an international registry // JAMA.– 2004.– Vol. 291.– P. 2727–2733.
Egan M.F., Kojima M., Callicott J.H. et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function // Cell.– 2003.– Vol. 112 (2).– P. 257–269. doi: https://doi.org/10.1016/s0092-8674(03)00035-7
Feng N., Huke S., Zhu G. et al. Constitutive BDNF/TrkB signaling is required for normal cardiac contraction and relaxation // Proc. Natl. Acad. Sci. USA.– 2015.– Vol. 112 (6).– P. 1880–1885. doi: https://doi.org/10.1073/pnas.1417949112.
Hayase M., Yoda S., Hatta T. et al. Prognostic Significance of the Residual SYNTAX Score and Ischemic Reduction Detected with Nuclear Cardiology for Prediction of Major Cardiac Events after Revascularization // Intern. Med.– 2020. doi: https://doi.org/10.2169/internalmedicine.3397-19. [Epub ahead of print].
Horita N., Kaneko T. Genetic model selection for a case-control study and a meta-analysis // Meta Gene.– 2015.– Vol. 5.– P. 1–8. doi: https://doi.org/10.1016/j.mgene.2015.04.003. PMID: 26042205; PMCID: PMC4443430.
Ibanez B., James S., Agewall S. et al. ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC) // Eur. Heart J.– 2018.– Vol. 39 (2).– P. 119–177.
Jiang H., Wang R., Liu Y. et al. BDNF Val66Met polymorphism is associated with unstable angina // Clin. Chim. Acta.– 2009.– Vol. 400 (1-2).– P. 3–7. doi: https://doi.org/10.1016/j.cca.2008.10.017.
Jiang R., Babyak M.A., Brummett B.H. et al. Brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism is associated with disease severity and incidence of cardiovascular events in a patient cohort // Ameer. Heart J.– 2017.– Vol. 190.– P. 40–45. doi: https://doi.org/10.1016/j.ahj.2017.05.002.
Kim J.M., Stewart R., Kim S.Y. et al. Interaction between BDNF val66met polymorphism and personality on long-term cardiac outcomes in patients with acute coronary syndrome // PLoS One.– 2019.– Vol. 14 (12).– P. e0226802. doi: https://doi.org/10.1371/journal.pone.0226802.
László A., Lénárt L., Illésy L. et al. The role of neurotrophins in psychopathology and cardiovascular diseases: psychosomatic connections // J. Neural. Transm. (Vienna). 2019.– Vol. 126 (3).– P. 265–278. doi: https://doi.org/10.1007/s00702-019-01973-6
Levey A.S., Stevens L.A., Schmid C.H. et al., for the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A New Equation to Estimate Glomerular Filtration Rate // Ann. Intern. Med.– 2009.– Vol. 150.– P. 604–612. [PMCID: PMC2763564]
Liu Y.Q., Su G.B., Duan C.H. et al. Brain derived neurotrophic factor gene polymorphisms are associated with coronary artery disease related depression and antidepressant response // Mol. Med. Rep.– 2014.– Vol. 10 (6).– P. 3247–3253. doi: https://doi.org/10.3892/mmr.2014.2638.
Mach F., Baigent C., Catapano A.L. et al., ESC Scientific Document Group, 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) // Eur. Heart J.– 2020.– Vol. 41 (1).– P. 111–188. doi: https://doi.org/10.1093/eurheartj/ehz455.
Paradies V., Zheng H., Chan M.H.H. et al. Impact of time of onset of symptom of ST-segment elevation myocardial infarction on 1-year rehospitalization for heart failure and mortality // Amer. Heart J.– 2020.– Vol. 224.– P. 1–9. doi: https://doi.org/10.1016/j.ahj.2020.03.011.
Ponikowski P., Voors A.A., Anker S.D. et al. ESC Scientific Document Group. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC // Eur. J. Heart Fail.– 2016.– Vol. 18.– P. 891–975. doi: https://doi.org/10.1093/eurheartj/ehw128.
Skaper S.D. The biology of neurotrophins, signalling pathways, and functional peptide mimetics of neurotrophins and their receptors // CNS Neurol. Disord. Drug. Targets.– 2008.– Vol. 7 (1).– P. 46–62.
Sookaromdee P., Wiwanitkit V. Brain-derived neurotrophic factor as biomarker // Anatol. J. Cardiol.– 2020.– Vol. 23 (3).– P. 192. doi: https://doi.org/10.14744/AnatolJCardiol.2020.84699.
Suriyaprom K., Tungtrongchitr R., Thawnasom K. Measurement of the levels of leptin, BDNF associated with polymorphisms LEP G2548A, LEPR Gln223Arg and BDNF Val66Met in Thai with metabolic syndrome // Diabetol. Metab. Syndr.– 2014.– Vol. 6.– P. 6. doi: https://doi.org/10.1186/1758-5996-6-6.
Williams B., Mancia G., Spiering W. et al. ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension // Eur. Heart J.– 2018.– Vol. 39 (33).– P. 3021–3104. doi: https://doi.org/10.1093/eurheartj/ehy339.
Zhang C., Liu H., Wang H. et al. The Predictive Value of Potential Hematological Biomarkers in Acute Coronary Syndrome // Clin. Lab.– 2019.– Vol. 65 (10). doi: https://doi.org/10.7754/Clin.Lab.2019.181232.