ABSTRACT
Abstract INTRODUCTION: Among patients with Chagas disease, men have a higher risk of worse pathological symptoms than women. We aimed to explore the role of the Y chromosome in men diagnosed with Chagas disease and assess the relationship between their ancestry and disease status. METHODS In this comparative study, we analyzed 150 men with unrelated non-chagasic disease (nCD) and 150 men with unrelated chagasic disease (CD). We assessed the serological diagnosis of Chagas disease, biochemical parameters, thoracic X-rays, electrocardiogram, and transthoracic echocardiography and determined the haplogroup by analyzing a set of 17 microsatellites from the Y chromosome. We examined the associations between common Y chromosome haplogroups and the clinical parameters of risk by logistic regression. RESULTS For all patients, the most common haplogroups were R1b (43%), G2a (9%), and E1b1b (9%). The R1b and G2a haplogroup was more frequent in men with nCD and CD, respectively. As expected, we observed a high proportion of symptomatic patients in the CD group independent of the haplogroups. Men from both groups classified as having the R1b haplogroup showed less clinical evidence of disease. Multivariate analysis showed that CD patients without R1b were about five times more likely to have a cardio-thorax index >0.5% (OR [odds ratio] = 5.1, 95% CI [confidence interval] = 3.31-8.17). Men without the R1b haplogroup were 2.5 times more likely to show EcoCG alterations (OR = 2.50, 95% CI = 0.16-3.94). CONCLUSIONS: Our results provided evidence that the R1b haplogroup may have a potential protective cardiovascular effect for its carriers.
Subject(s)
Humans , Male , Female , Chagas Disease/complications , Chagas Disease/genetics , Cardiomyopathies , Haplotypes , Odds Ratio , Chromosomes, Human, Y/geneticsABSTRACT
Aims: Endothelin-1 (ET-1) is a potent vasoconstrictive peptide, and its activity is mediated by the type A receptor (EDNRA). This action may play a significant role in the etiology of hypertension. There are different works that shows an association between certain polymorphisms of endothelin axis and clinical phenotype of hypertension. We describe the genetic variability +138/ex1 insertion/deletion (I/D) adenosine (A) in the ET-1 gene and polymorphism thymidine/cytosine (T/C) His323His in the EDNRA gene associated at the clinical variability in hypertensive patients. Study Design: Observational, transversal and analytical study. Place and Duration of Study: Hypertension Service at the Internal Medicine Department of Córdoba Hospital, and Biochemical and Molecular Biology Department in School of Medicine, National University of Cordoba, Argentine. Patients considered hypertensive between April 2009 and April 2010. Methodology: Were assessed 136 patients serum lipid profiles, renal and hepatic functions and were taken Thoracic X-rays, electrocardiograms, and echocardiographs. DNA extracted from circulating leukocyte were used to analyze the polymorphisms of genes by PCR-RFLP. Results: For the polymorphisms of Receptor A from Endothelin -1 studied the presence of cytosine homozygous genotype was less frequent in males (P = .02). For both genders, the same genotype was associated to low plasma alkaline phosphatase activity and cholesterol levels. The presence of thymidine nucleotide allele correlated with plasma alkaline phosphatase activity and cholesterol levels. The Thymidine allele correlated with the degree of cardiovascular compromise (r = 0.54, P= .002). For the genetic variant in the ET-1 gene, the homozygous adenine deletion was associated to normal plasma levels of glutamate/pyruvate transaminase enzyme activity, uric acid concentration, cholesterol, and Low Density Lipoprotein in hypertensive subjects without clinical risk. Conclusion: We observed a gender-specific protective effect for EDNRA gene variations, the subjects that carried the TT genotype presented more aggressive symptomatology. These results show an association between plasmatic biochemical parameters, the clinical condition, and polymorphisms in the endothelin axis genes.
ABSTRACT
Diversos trabajos han observado asociación entre polimorfismos de un solo nucleótido (SNPs) de genes en diferentes cardiomiopatías. Con los avances biomédicos logrados a partir de la secuenciación del genoma humano, se ha logrado una mejor compresión de la patogénesis de diferentes nfermedades a partir de la identificación de marcadores genéticos de riesgo (polimorfismos relacionados con enfermedades). En este sentido poco se conoce de lo que sucede con la fisiopatogenia de la Miocardiopatía Chagásica Crónica. Cabe preguntar, sí la presencia de Trypanosoma cruzi (T.cruzi) es un factor determinante en la evolución hacia el deterioro de la función cardíaca y para contrarrestar la infección, el huésped, responde y activa un conjunto de mecanismos de defensa (inmunes e inflamatorias) que persisten en el tiempo. Podríamos atribuir parte de la responsabilidad de la variabilidad en la expresión de síntomas y evolución de la Enfermedad de Chagas a características genéticas propias de cada individuo que permiten que se pongan en marcha mecanismos moleculares adaptativos acorde a la composición genética del huésped, para poder sobrellevar la función cardíaca con la mayor normalidad y no poner en riesgo la vida. Desentrañar la incógnita de cuales son los polimorfismos de genes, que actúan como factores de riesgo e identificar fenotipos intermediarios es importante para comprender las claves de las vías metabólicas y fisiológicas involucradas en una enfermedad. La selección de la variable clínica y las características biológicas de los genes candidatos, para detectar un perfil de riesgo de evolución, constituye un conocimiento que surge de las investigaciones genéticas en una condición compleja como la Miocardiopatía chagásica.
Several studies have shown an association between single nucleotide polymorphisms of genes in Different cardiomyopathies. With biomedical advances achieved from the human genome sequencing, it has gained a better understanding of the pathogenesis of various diseases from the identification of genetic markers of risk (disease-related polymorphisms). Thus little is known about what happens to the pathogenesis of chronic Chagas cardiomyopathy. One may ask, if Cruzi Trypanosoma (T. cruzi), is a determining factor in the evolution of the deterioration of cardiac function and to counter the infection, the host responds and activates a series of macanismos defense (immune and inflammatory) that persist over time. We could attribute part of the responsibility of the variability in the expression of Symptoms, signs and evolution of Chagas disease, a genetic characteristics of each individual, which allow olecular mechanisms put in place adaptive according to thegenetic makeup of guest, in order to cope with heart function more normally and not life risking.Unraveling the mystery of what are the polymorphisms of genes, acting as risk factors and identify intermediate phenotypes, it is important to understand the physiological and metabolic pathways involved in a disease. The selection of the variable clinical and biological characteristics of the Candidate genes to detect a risk profile of evolution is a Knowledge that comes from genetic research in a complex condition as Chagas Cardiomyopathy.Many publications have been looking for clinical associations and genetic polymorphisms of genes encoding proteins related to immuno-inflammatory events, one of the main hypotheses explain the clinical presentation of Chagas cardiomyopathy, yet fail to define a risk or protective factor . The identification of molecules involved in important metabolic pathways can lead to potential targets for therapeutic intervention.