Análisis de la relación entre polimorfismos en regiones diana de micro-ARN y la enfermedad hepática alcohólica / Analysis of the relationship between interleukin polymorphisms within miRNA-binding regions and alcoholic liver disease

Introducción. El consumo de alcohol induce una respuesta inflamatoria mediada por los receptores de tipo Toll4 (TLR4) y el factor nuclear (NF)-?B, originando daño orgánico. Algunos micro-ARN (miARN) modulan la respuesta inflamatoria mediante retroalimentación negativa de mediadores como las interleucinas (IL). Así pues, polimorfismos en los genes de algunas IL localizados cerca de las dianas de los miARN podrían modificar el riesgo de daño orgánico inducido por el alcohol. Este estudio analizó la posible relación entre el alcoholismo o la enfermedad hepática alcohólica (EHA) y los polimorfismos IL12B 2124 G>T (rs1368439), IL16 5000 C>T (rs1131445), IL1R1 3114 C>T (rs3917328) y NFKB1 3400 A>G (rs4648143). Pacientes y métodos. Se incluyeron 301 pacientes alcohólicos varones y 156 voluntarios sanos varones. Los polimorfismos fueron genotipados mediante discriminación alélica utilizando el sistema de PCR TaqMan(R). Se compararon las frecuencias alélicas y genotípicas entre grupos y se realizó un análisis de regresión logística para dilucidar el modelo de herencia. Resultados. El análisis del polimorfismo de IL1R1 (rs3917328) mostró que la proporción de portadores del aleloT (genotipos CT y TT) era mayor en los controles sanos (9,7%) que en pacientes alcohólicos (6,5%, p=0,042). Sin embargo el análisis de regresión logística no mostró resultados significativos. No se encontraron diferencias significativas entre grupos con respecto al resto de polimorfismos estudiados. Conclusiones. Nuestro estudio describe, por primera vez, las frecuencias esperadas de polimorfismos en regiones diana de miARN en pacientes alcohólicos con y sin EHA. Serán necesarios nuevos estudios para aclarar la relevancia de estos polimorfismos en el desarrollo de alcoholismo o EHA

Introduction. Alcohol consumption promotes inflammation through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-?B pathway, leading to organic damage. Some micro-RNA (miRNA) molecules modulate this inflammatory response by downregulating TLR4/NF-?B pathway mediators, like interleukins (ILs). Thus, polymorphisms within IL genes located near miRNA binding sites could modify the risk of ethanol-induced damage. The present study analyzed potential relationships between alcoholism or alcoholic liver disease (ALD) and IL12B 2124 G>T (rs1368439), IL16 5000 C>T (rs1131445), IL1R1 3114 C>T (rs3917328), and NFKB1 3400 A>G (rs4648143) polymorphisms. Patients and methods. The study included 301 male alcoholic patients and 156 male healthy volunteers. Polymorphisms were genotyped using TaqMan(R) PCR assays for allelic discrimination. Allele and genotype frequencies were compared between groups. Logistic regression analysis was performed to analyze the inheritance model. Results. Analysis of the IL1R1 (rs3917328) polymorphism showed that the proportion of alleleT carriers (CT and TT genotypes) was higher in healthy controls (9.7%) than in alcoholic patients (6.5%; P=.042). However, multivariable logistic regression analyses did not yield a significant result. No differences between groups were found for other analyzed polymorphisms. Conclusions. Our study describes, for the first time, the expected frequencies of certain polymorphisms within miRNA-binding sites in alcoholic patients with and without ALD. Further studies should be developed to clarify the potential relevance of these polymorphisms in alcoholism and ALD development

Analysis of the relationship between interleukin polymorphisms within miRNA-binding regions and alcoholic liver disease. / Análisis de la relación entre polimorfismos en regiones diana de micro-ARN y la enfermedad hepática alcohólica.

INTRODUCTION: Alcohol consumption promotes inflammation through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-?B pathway, leading to organic damage. Some micro-RNA (miRNA) molecules modulate this inflammatory response by downregulating TLR4/NF-?B pathway mediators, like interleukins (ILs). Thus, polymorphisms within IL genes located near miRNA binding sites could modify the risk of ethanol-induced damage. The present study analyzed potential relationships between alcoholism or alcoholic liver disease (ALD) and IL12B 2124 G>T (rs1368439), IL16 5000 C>T (rs1131445), IL1R1 3114 C>T (rs3917328), and NFKB1 3400 A>G (rs4648143) polymorphisms. PATIENTS AND METHODS: The study included 301 male alcoholic patients and 156 male healthy volunteers. Polymorphisms were genotyped using TaqMan® PCR assays for allelic discrimination. Allele and genotype frequencies were compared between groups. Logistic regression analysis was performed to analyze the inheritance model. RESULTS: Analysis of the IL1R1 (rs3917328) polymorphism showed that the proportion of alleleT carriers (CT and TT genotypes) was higher in healthy controls (9.7%) than in alcoholic patients (6.5%; P=.042). However, multivariable logistic regression analyses did not yield a significant result. No differences between groups were found for other analyzed polymorphisms. CONCLUSIONS: Our study describes, for the first time, the expected frequencies of certain polymorphisms within miRNA-binding sites in alcoholic patients with and without ALD. Further studies should be developed to clarify the potential relevance of these polymorphisms in alcoholism and ALD development.

The role of the TERC-63G>A and TERT-1327C>T telomerase polymorphisms in the study of men with acute coronary syndrome.

AIM: Telomerase is a ribonucleoprotein that maintains telomere length. Telomeres and telomerase are involved in cellular ageing and have been connected to some ageing related diseases, like cardiovascular disease. Telomerase dysfunction could be the main underlying mechanism in this connection but this point is still unclear. The aim of this article is to investigate the possible influence of cellular ageing, measured by two telomerase polymorphisms, TERC-63G>A (rs2293607) and TERT-1327C>T (rs2735940), on the whole spectrum of acute coronary artery disease (CAD). METHODS: We studied 150 middle aged men admitted for an acute coronary syndrome (ACS). Cardiovascular risk factors prevalence was collected at admission. Severity variables analyzed were Killip class and number of vessels affected. Telomerase polymorphisms were studied by real time PCR in DNA samples extracted from peripheral blood leukocytes. Clinical follow-up had been developed for more than 600 days and a prognostic combined event was defined. RESULTS: C allele of TERT polymorphism was more prevalent among hypertensive patients (OR: 3.19; 95% CI: 1.37-7.42; P=0.006). None of polymorphisms showed any prognostic value or relation to CAD severity. CONCLUSION: Telomerase dysfunction could be involved in hypertension prevalence. This finding could support new screening strategies in high risk population. The two telomerase polymorphisms analyzed did not show any prognostic value or connection to CAD severity. However, further studies are required to determine the molecular mechanisms responsible for cellular ageing in ACS.

A genetic variant in the microRNA-146a gene is associated with susceptibility to alcohol use disorders.

BACKGROUND: Polymorphisms in the microRNA (miRNA) regulatory pathways are novel functional genetic variants whose association with alcoholism susceptibility has not been previously studied. Given the potential relationship between certain miRNAs and alcohol use disorders (AUDs), this study was designed to explore the association between two polymorphisms within hsa-miR-146a and hsa-miR-196a2 genes and susceptibility to these diseases. METHODS: Three hundred and one male patients with AUDs and 156 sex-matched healthy volunteers were enrolled. Polymorphisms were genotyped using TaqMan(®) PCR assays. Allele and genotype frequencies were compared between groups and logistic regression analysis was also performed to analyze the model of inheritance. RESULTS: There was a significantly higher prevalence of allele C carriers (47.8%) of the miR-146a G>C polymorphism (rs2910164) among patients with AUDs when compared with controls (35.9%), and multivariable logistic regression analysis showed that the C allele was associated with these AUDs (OR=1.615, 95% CI 1.067-2.442; P=0.023). Neither the genotype nor the allele distribution of miR-196a2 polymorphism (rs11614913) was significantly different between groups. CONCLUSIONS: This is the first genetic association study to explore the relationship of miRNA polymorphisms with AUDs and to show an association of the miR-146a C>G rs2910164 allelic variant with this disease.