Study of the H558R polymorphism of the SCN5A gene in the genesis of chagasic heart disease.

Abstract

Chagasic heart disease is a chronic inflammatory cardiomyopathy that represents the most frequent and severe clinical consequence of the infection in our environment. Given the fundamental role of the type V voltage dependent sodium channel (SCN5A) for cardiac electrophysiology, this gene has been examined in a wide range of populations and pathologies but has not been evaluated in patients with Chagas disease.

The aim of the present work was to establish a possible association between H558R polymorphism in the SCN5A gene, with clinical, electrocardiographic and echocardiographic parameters, in patients with positive serology, in order to explain the symptomatic heterogeneity and detect a risk profile.

In a case-control study, 95 individuals were studied: 70 seropositive and 25 seronegative. All participants signed an informed consent. An epidemiological clinical questionnaire, physical examination, ECG (frequency, rhythm, axis, conduction disorders) and echocardiogram (motility, systolic and diastolic function) were performed. An aliquot of blood was used to determine the serology (HAI and ELISA), and the DNA was isolated to identify the proposed polymorphism through polymerase chain reaction. We analyzed allele and genotype frequencies using χ2 test and logistic regression to calculate the odds ratio (OR). A value of p<0.05 was considered statistically significant.

H558R genotypic frequencies: 35.7% CC genotype, 48.5% CT and 15.8% TT. The CT genotype was also more frequent (48%) in seronegative patients. Symptoms and signs of decompensated heart failure predominated in this group. CC genotype carriers with negative serology presented major alterations in the ECG and ECO such as: AV block, prolonged QTc, cavity dilatation and deterioration of systolic function, without significant differences between the groups. Logistic regression analysis showed that the C allele was significantly associated with an increased risk of developing left atrial dilation (P = 0.049, OR = 2.77, CI = 1–7.76).

Greater susceptibility to myocardial damage was found among the carriers of the C allele of the H558R polymorphism, so that this allele could confer a greater risk of occurrence and progression of chagasic heart disease.