9p21 Locus Polymorphisms: Risk and Severity Factors of Coronary Artery Disease in Venezuelan Patients

Abstract Background: The 9p21 region is the most relevant locus associated with coronary heart disease in different populations. However, there are no studies that prove that this region is a risk factor in the Venezuelan population. Objectives: To analyze whether or not the 9p21 rs1333049 polymorphism is a risk factor for acute myocardial infarction (AMI) in Venezuelan patients, as well as to investigate its correlation with cardiovascular risk factors (CVRF), age of occurrence, type and severity of infarction, and the correlation of the rs10757274 polymorphism with severity of coronary artery disease. Methods: This was an association study, including 487 unrelated Venezuelan individuals, grouped in 354 patients with AMI and 133 controls. The rs1333049 and rs10757274 polymorphisms were determined using the polymerase chain reaction (PCR) technique with sequence-specific primers. The analysis of association was determined using the SNPStats tool. The continuous variable description and the correlations were performed using the SPSS statistical software. Significance was established at p<0.05. Results: A positive correlation was observed between the rs1333049 polymorphism and the presence of hypertension ( r: 0.145, p: 0.006), and between hypertension and heart infarction ( r: 0.318, p: <0.0001). A positive correlation was found between the rs10757274 polymorphism and the number of coronary vessels that presented obstructive lesions in patients aged ≤ 55 years ( r: 0.276, p: 0.0078). Conclusion: The rs1333049 polymorphism at the 9p21 locus is correlated with hypertension in Venezuelan patients, while the rs10757274 polymorphism is associated with the progression of coronary atherosclerosis, suggested by the correlation with the number of coronary vessels that presented significant obstructive lesions.

Polimorfismo de genes de citocinas: ¿factores de riesgo cardiovascular en la población venezolana? / Polymorphism of cytokine genes: cardiovascular risk factors in the Venezuelan population?

Resumen Objetivo: Examinar si los polimorfismos de los genes IL6, TNFA e IL10 representan un marcador de riesgo de infarto agudo de miocardio (IAM) y analizar su correlación con los factores de riesgo, la edad de ocurrencia y el tipo de IAM. Método: Estudio de asociación que incluyó 310 individuos venezolanos, no relacionados, agrupados en 190 pacientes con IAM y 120 controles con o sin factores de riesgo cardiovascular. Los polimorfismos IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629) e IL10-1082 A/G (rs1800896), -819 C/T (rs1800871) y -592 C/A (rs1800872) se determinaron utilizando la técnica reacción en cadena de la polimerasa con iniciadores de secuencias específicas. Resultados: La comparación de frecuencias genotípicas y alélicas, mediante el análisis de regresión logística ajustado para los factores de riesgo, mostró una frecuencia significativamente incrementada de la combinación de genotipos G/G-A/A de la variante TNFA-308 G/A (odds ratio [OR]: 3.8; p = 0.00007), GG/-C/C de la variante IL6-174 G/C (OR: 2.3; p = 0.009), A/G-G/G de la variante IL10-1082 A/G (OR: 3.8; p = 0.00001) y del haplotipo GCC de IL10 (OR: 3.71; p = 0.0053) en los pacientes con IAM con respecto a los controles. Se observaron interacciones entre los polimorfismos IL10-1082 A/G y TNFA-308 G/A e hipertensión. Conclusiones: La asociación de las variantes de los genes TNFA, IL6 e IL10 con IAM sugiere que el desbalance en la producción de citocinas promueve un proceso inflamatorio exacerbado, apoyando el papel fundamental de la inflamación en todas las etapas del proceso aterosclerótico.

Abstract Objective: To examine whether the polymorphisms of the IL6, TNFA and IL10 genes represent a risk marker for acute myocardial infarction (AMI) and to analyze their correlation with risk factors, age of occurrence and type of AMI. Method: Association study that included 310 unrelated Venezuelan individuals, grouped in 190 patients with AMI and 120 controls with or without cardiovascular risk factors. The IL6-174 G/C (rs1800795), TNFA -308 G/A (rs1800629), and IL10-1082 A/G (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms were determined using the polymerase chain reaction technique with sequence-specific primers. Results: Comparison of genotypic and allelic frequencies, using adjusted logistic regression analysis for risk factors, showed a significantly increased frequency of the genotype combination G/G-A/A of TNFA-308 G/A (odds ratio [OR]: 3.8; p = 0.00007), GG/-C/C of IL6-174 G/C (OR: 2.3; p = 0.009), A/G-G/G of IL10-1082 A/G (OR: 3.8; p = 0.00001) and the GCC haplotype of IL10 (OR: 3.71; p = 0.0053) in infarcted patients compared to controls. Interactions between the IL10-1082 A/G and TNFA-308 G/A polymorphisms and hypertension were observed. Conclusions: The association of the variants of the TNFA, IL6 and IL10 genes with AMI suggest that the imbalance in the production of cytokines promotes an exacerbated inflammatory process, supporting the fundamental role of inflammation in all stages of the atherosclerotic process.

Polimorfismo de genes de citocinas: ¿factores de riesgo cardiovascular en la población venezolana? / Polymorphism of cytokine genes: cardiovascular risk factors in the Venezuelan population?

Objective: To examine whether the polymorphisms of the IL6, TNFA and IL10 genes represent a risk marker for acute myocardial infarction (AMI) and to analyze their correlation with risk factors, age of occurrence and type of AMI. Method: Association study that included 310 unrelated Venezuelan individuals, grouped in 190 patients with AMI and 120 controls with or without cardiovascular risk factors. The IL6-174 G/C (rs1800795), TNFA -308 G/A (rs1800629), and IL10-1082 A/G (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms were determined using the polymerase chain reaction technique with sequence-specific primers. Results: Comparison of genotypic and allelic frequencies, using adjusted logistic regression analysis for risk factors, showed a significantly increased frequency of the genotype combination G/G-A/A of TNFA-308 G/A (odds ratio [OR]: 3.8; p = 0.00007), GG/-C/C of IL6-174 G/C (OR: 2.3; p = 0.009), A/G-G/G of IL10-1082 A/G (OR: 3.8; p = 0.00001) and the GCC haplotype of IL10 (OR: 3.71; p = 0.0053) in infarcted patients compared to controls. Interactions between the IL10-1082 A/G and TNFA-308 G/A polymorphisms and hypertension were observed. Conclusions: The association of the variants of the TNFA, IL6 and IL10 genes with AMI suggest that the imbalance in the production of cytokines promotes an exacerbated inflammatory process, supporting the fundamental role of inflammation in all stages of the atherosclerotic process.

Objetivo: Examinar si los polimorfismos de los genes IL6, TNFA e IL10 representan un marcador de riesgo de infarto agudo de miocardio (IAM) y analizar su correlación con los factores de riesgo, la edad de ocurrencia y el tipo de IAM. Método: Estudio de asociación que incluyó 310 individuos venezolanos, no relacionados, agrupados en 190 pacientes con IAM y 120 controles con o sin factores de riesgo cardiovascular. Los polimorfismos IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629) e IL10-1082 A/G (rs1800896), -819 C/T (rs1800871) y -592 C/A (rs1800872) se determinaron utilizando la técnica reacción en cadena de la polimerasa con iniciadores de secuencias específicas. Resultados: La comparación de frecuencias genotípicas y alélicas, mediante el análisis de regresión logística ajustado para los factores de riesgo, mostró una frecuencia significativamente incrementada de la combinación de genotipos G/G-A/A de la variante TNFA-308 G/A (odds ratio [OR]: 3.8; p = 0.00007), GG/-C/C de la variante IL6-174 G/C (OR: 2.3; p = 0.009), A/G-G/G de la variante IL10-1082 A/G (OR: 3.8; p = 0.00001) y del haplotipo GCC de IL10 (OR: 3.71; p = 0.0053) en los pacientes con IAM con respecto a los controles. Se observaron interacciones entre los polimorfismos IL10-1082 A/G y TNFA-308 G/A e hipertensión. Conclusiones: La asociación de las variantes de los genes TNFA, IL6 e IL10 con IAM sugiere que el desbalance en la producción de citocinas promueve un proceso inflamatorio exacerbado, apoyando el papel fundamental de la inflamación en todas las etapas del proceso aterosclerótico.

In Vitro Assessment of Plants Growing in Cuba Belonging to Solanaceae Family Against Leishmania amazonensis.

In this study, an in vitro antileishmanial assessment of plant extracts from 12 genera and 46 species growing in Cuba belonging to Solanaceae family was performed. A total of 226 extracts were screened against promastigotes of Leishmania amazonensis, and cytotoxicity of active extracts [median inhibitory concentration (IC50 ) promastigotes <100 µg/mL] was determined on peritoneal macrophage from BALB/c mice. Extracts that showed selective index >5 were then assayed against intracellular amastigote. Metabolomics analysis of promissory extracts was performed using chemical profile obtained by ultra performance liquid chromatography. Only 11 extracts (4.9%) from nine plants were selected as potentially actives: Brunfelsia cestroides A. Rich, Capsicum annuum L., Capsicum chinense Jacq., Cestrum nocturnum L., Nicotiana plumbaginifolia Viv., Solanum havanense Jacq., Solanum myriacanthum Dunal, Solanum nudum Dunal and Solanum seaforthianum And., with IC50 < 50 µg/mL and selectivity index >5. Metabolomics analysis demonstrated significant differences in the chemical profiles with an average of 42.8 (range 31-88) compounds from m/z 104 to 1477, which demonstrated the complex mixture of compounds. In addition, no common markers among active extracts were identified. The results demonstrate the importance of the Solanaceae family to search new antileishmanial agents, particularly in unexplored species of this family. Copyright © 2016 John Wiley & Sons, Ltd.

Cromomicosis por cladophialophora carrionii: características citogenéticas básicas: comunicación preliminar / Chromomycosis due to cladophilophora carrionii: basic cytogenetic characters: preliminary report

Hay estudios de diversa indole sobre pacientes con cromomicosis cladophialophora carrionni del foco endémico del estado Falcón (Venezuela), pero no ha sido estudiada la genética de ellos. Demostrar alteraciones citogenéticas relacionadas con la enfermedad y comparar su frecuencia en pobladores afectados y no afectados por esta enfermedad. Fueron seleccionados 11 pacientes consanguíneos con diagnóstico o historia de cromomicosis para el grupo de casos y 13 controles no consanguíneos, sin historia ni diagnóstico de la enfermedad. Los estudios citogenéticos se realizaron en muestras se sangre periférica. Ciento por ciento de los casos presentó alteraciones citogenéticas y no se encontraron en ninguno de los controles. Estas alteraciones fueron: ruptura de cromátides en 82 por ciento, pérdidas cromosómicas en 17 por ciento, ganancias cromosómicas en 7 por ciento y los cromososmas 1 y 6 fueron los más frecuentemente asociados a polimorfismo. Se demostró la presencia de alteraciones citogenéticas en 100 por ciento de los casos mientras que éstas no se encontraron en los controles. El patrón encontrado se puede asociar con otras enfermedades autosómicas recesivas por lo que esta probabilidad debe ser estudiada para definir si es el gatillo o la condición poligénica que permite la mayor suceptibilidad a la enfermedad fúngica