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| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Blanco Sobrino, Susana | - |
| dc.date.accessioned | 2025-02-12T14:59:57Z | - |
| dc.date.available | 2025-02-12T14:59:57Z | - |
| dc.date.issued | 2022-11 | - |
| dc.identifier.citation | Blanco Sobrino, Susana (2022) Cardiopatía isquémica y su asociación con los genes de receptores tipo TOLL (TLR2 y TLR4). Tesis Doctoral que se Presenta para Optar al título de Ciencias de la Salud. Universidad Central de Venezuela. Tutor: Fernández Mestre, Mercedes | en_US |
| dc.identifier.uri | http://hdl.handle.net/10872/23428 | - |
| dc.description.abstract | Fundamentación: La Organización Panamericana de la Salud (OPS) señala que Venezuela es el país más rezagado en el cumplimiento de las metas de reducción de la mortalidad prematura por enfermedad cardiovascular. La cardiopatía isquémica (CI), particularmente el infarto agudo de miocardio (IAM), es la causa número uno de la mortalidad cardiovascular, siendo responsable del 25% de la mortalidad en la población adulta venezolana. Objetivo: Determinar la asociación entre la cardiopatía isquémica y la variabilidad de los genes de receptores tipo Toll (TLR2 y TLR4) en pacientes con síndrome coronario agudo Métodos: Estudio descriptivo, de prevalencia, de asociación y correlacional, que incluyó 209 individuos venezolanos, no relacionados, clasificados en dos grupos. Pacientes con diagnóstico de IAM (n=75) e individuos aparentemente sanos (n=134), con o sin factores de riesgo cardiovascular (FRCV). A cada uno de los individuos se les extrajo 5 mL de sangre, a partir de la cual se extrajo el ADN genómico. La determinación de los polimorfismos Pro631His (rs5743704) y Arg753Gln (rs5743708) del gen TLR2, Arg299Gly (rs4986790) y Thr399Ile (4986791) del gen TLR4, se realizó utilizando la técnica PCR-SSP. Las frecuencias de los polimorfismos, el equilibrio de Hardy-Weinberg y el modelo de herencia se determinaron con el programa SNPStats. Las diferencias de frecuencias entre los grupos fueron estimadas por la prueba de Ji-cuadrado y la fuerza de asociación se determinó como Odds Ratio. El análisis de correlación entre los polimorfismos, FRCV y severidad se determinó a través del coeficiente de correlación de Pearson. Resultados: En los individuos que sufrieron IAM temprano ( 55 años), los principales FRCV fueron el sexo (masculino), la hipertensión y el sedentarismo. Los pacientes con genotipos con por lo menos un alelo mutado (C/T + T/T) del polimorfismo TLR4 rs4986791 (Thr399Ile) son más propensos a sufrir IAM. El análisis de correlación sugiere que la asociación del polimorfismo rs4986791 (Thr399Ile) del gen TLR4 es independiente de FRCV, explicando el desarrollo de IAM temprano. Conclusión: Los FRCV y la variabilidad genética juegan un papel importante en el desarrollo de la CI. | en_US |
| dc.description.sponsorship | Background: The Pan American Health Organization (PAHO) estimates that Venezuela is one of the slowest nations to meet the global goals of reducing premature mortality due to cardiovascular disease. Ischemic heart disease (IHD), specifically acute myocardial infarction (AMI), is the leading cause of cardiovascular mortality since it is responsible for 25% of the mortality rate in Venezuelan's adult population. Objective: To determine the association between ischemic heart disease (IHD) and Toll-like receptor genes (TLR2 and TLR4) variability in patients with acute coronary syndrome (ACS). Methods: This is a prevalence, association, correlational, and descriptive study which included 209 unrelated Venezuelan individuals organized into two groups: Patients with an AMI diagnosis (n=75) and healthy individuals (n=134) with or without cardiovascular risk factors (CVRFs). The procedure required the extraction of 5mL of blood from each individual to extract their genomic DNA. The determination of the Pro631His (rs5743704) and Arg753Gln (rs5743708) polymorphisms of the TLR2 gene, Arg299Gly (rs4986790), and Thr399Ile (4986791) of the TLR4 gene were performed by using the PCR-SSP technique. The SNPStats program was used to determine the polymorphism's frequency, the Hardy-Weinberg equilibrium, and the inheritance model. The frequencies among the different groups were estimated by using the Chi-squared test, while the strength of the association was determined by Odds Ratio. The correlation analysis between the polymorphisms, CVRFs, and severity of disease was determined through the Pearson correlation coefficient. Results: In individuals who suffered early AMI (≥55 years), the main CVRFs were the male sex, hypertension, and a sedentary lifestyle. Patients with genotypes with at least one mutated allele (C/T + T/T) of the TLR4 rs4986791 (Thr399Ile) polymorphism are more prone to AMI. The correlation analysis suggests that the association of the rs4986791 (Thr399Ile) polymorphism of the TLR4 gene is independent of CVRFs, which explains the development of early AMI. Conclusion: CVRF and genetic variability play a major role in the development of I Objective: To determine the association between ischemic heart disease (IHD) and Toll-like receptor genes (TLR2 and TLR4) variability in patients with acute coronary syndrome (ACS). Methods: This is a prevalence, association, correlational, and descriptive study which included 209 unrelated Venezuelan individuals organized into two groups: Patients with an AMI diagnosis (n=75) and healthy individuals (n=134) with or without cardiovascular risk factors (CVRFs). The procedure required the extraction of 5mL of blood from each individual to extract their genomic DNA. The determination of the Pro631His (rs5743704) and Arg753Gln (rs5743708) polymorphisms of the TLR2 gene, Arg299Gly (rs4986790), and Thr399Ile (4986791) of the TLR4 gene were performed by using the PCR-SSP technique. The SNPStats program was used to determine the polymorphism's frequency, the Hardy-Weinberg equilibrium, and the inheritance model. The frequencies among the different groups were estimated by using the Chi-squared test, while the strength of the association was determined by Odds Ratio. The correlation analysis between the polymorphisms, CVRFs, and severity of disease was determined through the Pearson correlation coefficient. Results: In individuals who suffered early AMI (≥55 years), the main CVRFs were the male sex, hypertension, and a sedentary lifestyle. Patients with genotypes with at least one mutated allele (C/T + T/T) of the TLR4 rs4986791 (Thr399Ile) polymorphism are more prone to AMI. The correlation analysis suggests that the association of the rs4986791 (Thr399Ile) polymorphism of the TLR4 gene is independent of CVRFs, which explains the development of early AMI. Conclusion: CVRF and genetic variability play a major role in the development of IHD. | en_US |
| dc.subject | TLR | en_US |
| dc.subject | Polimorfismo | en_US |
| dc.subject | Cardiopatía Isquémica | en_US |
| dc.subject | Infarto Agudo de Miocardio | en_US |
| dc.subject | Factores de Riesgo Cardiovascular | en_US |
| dc.subject | Tesis Doctoral | en_US |
| dc.subject | Ciencias de la Salud | en_US |
| dc.subject | Facultad de Medicina | en_US |
| dc.subject | UCV | en_US |
| dc.title | Cardiopatía isquémica y su asociación con los genes de receptores tipo TOLL (TLR2 y TLR4) | en_US |
| dc.type | Thesis | en_US |
| Appears in Collections: | Doctoral | |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| 1. Tesis Doctoral Dra. Susana Blanco.pdf | 3.25 MB | Adobe PDF | View/Open |
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