Evaluation of Apolipoprotein-A1 genetic polymorphisms as biomarkers for Chagas cardiomyopathy in patients from Córdoba, Argentina

Abstract

Background Chagas disease frequently leads to chronic chagasic cardiomyopathy, a major cause of mortality in endemic regions. Host genetic factors could potentially play a role in the progression of heart disease. This study aimed to assess the association between APOA1 polymorphisms and chagasic cardiomyopathy. Methods and results A retrospective, observational study was conducted on 158 Trypanosoma cruzi-infected patients from Córdoba, Argentina, classified into three groups: G1 (without heart disease), G2 (with mild heart disease), and G3 (with severe heart disease). APOA1 G-75A and C+83T polymorphisms were genotyped using PCR-RFLP. No significant association was found between APOA1 polymorphisms and the overall presence or severity of chagasic cardiomyopathy (G1 vs. G2+G3; G2 vs. G3). However, in subgroup analyses, the −75/A allele was associated with an increased risk of ventricular extrasystoles (OR=2.4; 95% CI: 1.04–5.53). Furthermore, sex- and age-stratified analyses revealed specific associations with arrhythmias for both the −75/A and +83/T variants. Notably, the heterozygous genotype for G-75A was associated with the progression of chagasic cardiac alterations in women (-75GA: OR=4.35; 95% CI: 1.11–17.04). Conclusion APOA1 genetic variants are not major determinants of chagasic cardiomyopathy at a population level in this cohort. However, our findings suggest they may act as modifiers of disease phenotype, modulating susceptibility to specific arrhythmic manifestations, particularly in demographic subgroups defined by sex and age. These results highlight the complex genetic architecture of Chagas disease and underline the need for further studies in larger cohorts to confirm these associations and elucidate their clinical relevance.