SCN5A Gene Variants Influence the Predisposition to Chronic Chagasic Cardiac Alterations

VELÁZQUEZ D; RIVAROLA HW; BLASCO R; TABARES S; LO PRESTI MS; STRAUSS M; SEMBAJ A; PAGLINI P

Buenos Aires

Congreso; 16th World Congress of Arrhythmias; 2019

Sociedad Argentina de Electrofisiología Cardíaca y World Society of Arrhythmias

Host genetic factors are probably determinants of the variable progression of Chagas disease (ChD). Two polymorphisms of the voltage-gated sodium channel α-subunit (SCN5A) gene (H558R and A572D) in chagasic patients were studied in order to determine the possible role of SCN5A gene variants in the susceptibility to infection by Trypanosoma cruzi and/or development of chronic chagasic cardiac alterations. A total of 95 Argentinian individuals from an endemic region for ChD were included. Clinical evaluation, electrocardiogram (ECG) and echocardiogram (Echo) were performed to detect any conduction and/or structural alteration. H558R and A572D polymorphisms were detected by PCR. Patients were classified as follows: G1: without ECG and/or Echo alterations, G2: with ECG alterations and G3: with ECG and Echo alterations. Cardiac alterations were more frequent in G2+G3 seropositive patients; this was not the case in seronegative patients with the exception of left atrial enlargement (LAE). H558R polymorphism was associated with predisposition to LAE in seropositive patients (P = 0.0273) but not in seronegative ones. Furthermore, allele C was significantly associated with an increased risk for developing LAE (P = 0.049, OR = 2.77, CI = 1?7.76). The allelic and genotypic frequencies for A572D were not statistically different when comparing seropositive G1 vs. G2+G3 patients and no association were found with the clinical characteristics. Our results contribute to the elucidation of the molecular mechanism underlying ChD and suggest that SCN5A-H558R variants could be associated with a susceptibility to the development of chronic chagasic cardiomyopathy.