Analysis of DNA polymorphisms in the Endothelin-1 and Superoxide dismutase-Mg genes and their relationship with the evolution of the Chagasic Cardiomyopathy

O. LASSEN, F. QUINTIERO , S. TABARES , J. HERRERA , A. GARUTTI, G.DOTTO , R. SOSA , R. GALERANO , A.

Buenos Aires

Congreso; World Congress of Cardiology; 2008

Federación Argentina de Cardiología y Sociedad Argentina de Cardiología

ANALYSIS OF DNA POLYMORPHISMS IN THE ENDOTHELIN-1 AND SUPEROXIDE DISMUTASE-MG GENES AND THEIR RELATIONSHIP WITH THE EVOLUTION OF THE CHAGASIC CARDIOMYOPATHY O. Lassen 2, F. Quintiero 1,  S. Tabares 1, J. Herrera 1, A. Garutti 3, G.Dotto 3, R. Sosa 2, R. Galerano 2, A. Sembaj 1.   1 Biocheistry and Molecular Biology Deparment. School of Medicine, National University of Córdoba  2 Unit of Internal Medicine Nº3. School of Medicine, National University of Córdoba, Córdoba Public Hospital  3 Central Laboratory of biochemistry, Córdoba Public Hospital Approximately 30% of Trypanosoma cruzi (Tc) infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory cardiomyopathy whose symptoms appears decades after the primoinfection, a third part of these patients suffer fatal progression. Heterogeneity of the clinical expression of the symptoms of Chagas disease suggests that several genetic factors are involved in the pathogenesis. It is know that 90 % of the human phenotypic diversity is generated by DNA single nucleotide polymorphism (SNP). There is an increasing interest in knowing whether genetic polymorphisms of genes encoding factors involved in the clinical manifestations, participate in the progression and/or severity of the disease. Several studies have reported genetic markers of susceptibility in the development of Chagas’ cardiomyopathy. Based on these data, we propose to study the functional polymorphism Ala-9Val of the Superoxide dismutase Mn dependent (SOD-Mn) gene, and the polymorphism 138 /ex1ins/delA of the endothelin-1 (ET-1) gene using RFLP analysis of PCR DNA fragments amplified from genomic DNA extracted from circulating leukocytes of patients attending the Cordoba Hospital. All patients were investigated for Tc infection in serum and evaluated by ECG and EcoCG. Based on the clinical records they were classified in Group 1: 40 patients with chronic Chagas’ cardiomyopathy; Group 2: 45 patients with cardiomyopathy without Chagas infection, and Group 3: 23 heathy individuals. The statistics analysis of the Ala-9Val polymorphism in SOD.Mn gene showed that healthy individuals are in population equilibrium, and an excess of heterozygotes in cardiac patients was observed. We found no difference in genotypes distribution and allelic frequency between chagasic and non chagasic patients, however the heterozygote genotype was more frequent in patient’s (p ≤ 0,005) and the allele encoding Alanine was significantly more frequent among the cardiologically less affected patients.