The role of single nucleotide polymorphism of val66met (rs6265) of the brain-derived neurotropic factor in formation of endpoints after st-segment elevation myocardial infarction

Abstract Background The single nucleotide polymorphism (SNP) Val66Met (rs6265) of the brain-derived neurotrophic factor (BDNF) gene is a possible candidate that is associated with the development of psychopathology and combines it with cardiovascular events. Purpose To research the possible associations of single-nucleotide polymorphism of Val66Met BDNF gene with the occurrence of endpoints after 6 months of follow-up after ST segment elevation myocardial infarction (STEMI). Methods 256 acute STEMI patients after successful primary percutaneous coronary intervention (PCI) were enrolled in the study. TIMI III blood flow restoring through culprit artery was determined. The study of SNP of Val66Met (rs6265) of the BDNF gene was performed by real-time polymerase chain reaction. The emotional state of the patients and its relationship with stress were assessed with the questionnaire “Depression, Anxiety and Stress-21”. All acute STEMI patients received adjuvant treatment due to current ESC recommendations. All procedures performed in the study involving human participants were in accordance with the ethical standards and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards and approved by the local ethics committee. Written inform consent was obtained from each patient. The primary endpoint was combined event (follow-up major adverse cardiac events – MACEs and hospitalization) that occurred within 6-month of the discharge from the hospital. MACEs were defined as the composite of CV death, recurrent angina, newly diagnosed heart failure. Results The frequency of genotypes Val66Met gene for BDNF in STEMI patients (n=256) was the following: 66ValVal=74.2% (n=190), 66ValMet + 66MetMet – 25.8% (n=66). The 66ValMet + 66MetMet polymorphism in the BDNF gene, stress and anxiety on 10–14 days before the event, as well as reduced left ventricular ejection fraction (LVEF), were independently associated with combined 6 months clinical end point after STEMI. Severity of depression according to depression scale was more profound in individuals with 66ValMet+66MetMet polymorphysms in BDNF gene (P=0.045) than in patients with 66ValVal genotype. Univariate and multivariate linear regressions has shown that 66ValMet+66MetMet genotype in BDNF gene, anxiety and stress before event, LVEF had independent power on dependent variable entitled combined end point after 6 month observation for STEMI patients with successful revascularization (P=0.0395). Kaplan-Meier curves demonstrated that STEMI patients with 66ValVal genotype in BDNF gene had a lower accumulation of combined end point compared with acute STEMI patients with 66ValMet+66ValMet polymorphism (Cox-criterion, P=0.019; log-rang criterion, P=0.03). Conclusion The Val66Met polymorphism in BDNF gene was found as an independent predictor for combined 6-month clinical end points after acute STEMI treated primary PCI. Funding Acknowledgement Type of funding source: None

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The role of single nucleotide polymorphism Val66Met in BDNF gene in the formation of end points after ST segment elevation myocardial infarction

Ukrains'kyi Visnyk Psykhonevrolohii ◽

10.36927/2079-0325-v27-is3-2019-3 ◽

2019 ◽

Vol 27 (3) ◽

pp. 19-25

Author(s):

Olga Petyunina ◽

Mykola Kopytsya ◽

Olga Skrynnyk

Keyword(s):

Myocardial Infarction ◽

Single Nucleotide Polymorphism ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Bdnf Gene ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

St Segment Elevation ◽

Segment Elevation Myocardial Infarction ◽

St Segment

The purpose of this study was to research the possible associations of single-nucleotide polymorphism of Val66Met BDNF gene with the occurrence of endpoints after 6 months of follow-up after a myocardial infarction with ST elevation segment — ST segment elevation myocardial infarction (STEMI). To participate in the study, 256 patients which met all the inclusion criteria were hospitalized in the department of intensive care, State Institution “L. T. Malaya Therapy National Institute NAMSU” from January 2016 to February 2019. Blood fl ow to all patients was restored at the level TIMI III. The frequency of genotypes Val66Met gene for BDNF in STEMI patients (n = 256) was the following: 66ValVal — 74.2 % (n = 190), 66ValMet + 66MetMet — 25.8 % (n = 66). The study of single-nucleotide polymorphism of Val66Met gene BDNF (rs6265) was performed by real-time polymerase chain reaction using the “TacMan TMSNP Genotyping Assays” production of Thermo Fisher Scientifi c Assay IDC_11592758_1. The emotional state of the patients and its relationship with stress were assessed with the questionnaire “Depression, Anxiety and Stress Scale-21”. It turned out that the 66ValMet + 66MetMet polymorphism of the BDNF gene, stress and anxiety 10—14 days before the event, as well as reduced left ventricular ejection fraction, are associated with an unfavorable prognosis of the combined end point 6 months after STEMI and are its independent predictors.

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Faculty Opinions recommendation of Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718525603.793524399 ◽

2016 ◽

Author(s):

Ignatia Van den Veyver

Keyword(s):

Single Nucleotide Polymorphism ◽

Clinical Experience ◽

Large Scale ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Aneuploidy Testing

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A vascular endothelial growth factor A genetic variant is associated with improved ventricular function and transplant-free survival after surgery for non-syndromic CHD

Cardiology in the Young ◽

10.1017/s1047951117001391 ◽

2017 ◽

Vol 28 (1) ◽

pp. 39-45 ◽

Cited By ~ 5

Author(s):

Constantine D. Mavroudis ◽

Daniel Seung Kim ◽

Nancy Burnham ◽

Alexandra H. Morss ◽

Jerry H. Kim ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Single Nucleotide Polymorphism ◽

Growth Factor ◽

Ventricular Function ◽

Vascular Endothelial ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Free Survival ◽

Endothelial Growth Factor

AbstractBackgroundWe have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.MethodsThis study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.ResultsGenetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).ConclusionsThese data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.

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The role of Val66Met single nucleotide polymorphism in brain-derived neurotropic factor gene in prediction of adverse outcomes after ST-segment elevation myocardial infarction

Heart and Mind ◽

10.4103/hm.hm_40_19 ◽

2019 ◽

Vol 3 (1) ◽

pp. 7

Author(s):

AlexanderE Berezin ◽

OlgaV Petyunina ◽

MykolaP Kopytsya ◽

OlgaV Skrynnyk

Keyword(s):

Myocardial Infarction ◽

Adverse Outcomes ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Factor Gene ◽

St Segment Elevation ◽

Segment Elevation Myocardial Infarction ◽

St Segment ◽

Neurotropic Factor

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Single Nucleotide Polymorphism p.Val66Met in BDNF Gene in the Czech Population

Česká a slovenská neurologie a neurochirurgie ◽

10.14735/amcsnn2017597 ◽

2017 ◽

Vol 80/113 (5) ◽

pp. 597-600

Author(s):

Sylwia Walczysková ◽

Pavel Ressner ◽

Šárka Hilscherová

Keyword(s):

Single Nucleotide Polymorphism ◽

Bdnf Gene ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Czech Population

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The role of single nucleotide polymorphism of IL-6 and IL-10 cytokine on pain severity and pain relief after radiotherapy in multiple myeloma patients with painful bone destructions

Genetika ◽

10.2298/gensr1402455r ◽

2014 ◽

Vol 46 (2) ◽

pp. 455-469 ◽

Cited By ~ 1

Author(s):

Milda Rudzianskiene ◽

Arturas Inciura ◽

Elona Juozaityte ◽

Rolandas Gerbutavicius ◽

Renata Simoliuniene ◽

...

Keyword(s):

Multiple Myeloma ◽

Single Nucleotide Polymorphism ◽

Pain Relief ◽

Promoter Region ◽

Severe Pain ◽

Gene Promoter ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Analgesic Response

Multiple myeloma (MM) cells interact with bone marrow stromal cells stimulating transcription and secretion of cytokines like IL-6 and IL-10, which are implicated in the progression and dissemination of MM. Regulation of cytokines secretion is under genetic control through genetic polymorphisms in their coding and promoter sequences. It seems that single nucleotide polymorphism (SNP) in the promoter region of various genes may regulate the plasma concentrations of cytokines. Cytokines could be also hypothesized to function as pain modulators as peripheral nociceptors are sensitized by cytokines. The aim was to determine if the SNP of IL-6 and IL-10 cytokines could influence the analgesic response of radiotherapy in the treatment of painful bone destructions in MM patients. 30 patients (19 women and 11 men, median age: 67 years) with MM and painful bone destructions were treated with palliative radiotherapy. Pain was evaluated according to the visual analogue scale and analgesics intake. Pain scores and analgesics use were measured prior to radiotherapy as well as 4, 12 and 24 weeks afterward. Opioid analgesics were converted to the morphine-equivalent daily dose (MEDD). Genomic DNA was extracted from peripheral blood leukocytes and IL-6 and IL-10 gene promoter polymorphisms were analysed with polymerase chain reaction. 60% of patients reported severe pain prior to radiotherapy, which decreased to 13% at the first follow-up visit (p <0.001). The MEDD on admission to the hospital was 75 mg/day which decreased to 46 mg/day at the first follow-up visit (p = 0.033). A significant parameter in pain relief was: age < 65 years (p=0.029). We analysed 6 SNPs in the gene promoter region of IL-6 (-597 G/A, -572 G/C, -174 G/C) and IL-10 (-592 A/C, -819 C/T, -1082 A/G) as well as their relation with pain severity and analgesic consumption. Patients who are IL-10 -1082 A/G carriers are prone to respond better to radiotherapy than other patients (p<0.05). A borderline association was noted for patients who are IL-6 -597 A/A and G/G carriers - assumed to be at higher risk for severe pain prior to radiotherapy (p=0.07) while for patients who are IL-10 - 1082 A/A carries: the median pain score decreased faster (p=0.08). Patients with genotypes IL-6 -597 A/A and IL-6 -174 C/C required a smaller dose of opioids (p=0.06). SNP of IL-6 and IL-10 cytokines can influence the analgesic response of radiotherapy. Patients with genotype IL-10 -1082 A/G respond better to radiotherapy.

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Single nuclear polymorphism Val66Met (rs6265) of brain derived neurotrophic factor gene in prognostication of outcomes after ST segment elevation myocardial infarction

Ukrainian Journal of Cardiology ◽

10.31928/1608-635x-2020.3.4959 ◽

2020 ◽

Vol 27 (3) ◽

pp. 49-59

Author(s):

O. V. Petyunina ◽

M. P. Kopytsya ◽

О. Е. Berezin

Keyword(s):

Coronary Intervention ◽

Syntax Score ◽

Bdnf Gene ◽

St Segment Elevation ◽

End Point ◽

Timi Score ◽

St Segment ◽

Percutaneous Coronary ◽

Nuclear Polymorphism ◽

Single Nuclear Polymorphism

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.

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