Preliminary study between Y chromosome haplogroups and chagasic cardiomyopathy manifestations in patients with Chagas disease

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.

Plasmatic Biochemical Variables Associated with Polymorphisms in the Endothelin-1 and Endothelin-1 Receptor a Genes in Hypertensive Patients: Pilot Study.

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.