Apolipoportein-A1 gene polymorphisms in patients with positive serology for Chagas. Preliminary results

Abstract

Over the last few decades, several markers of chagasic cardiomyopathy progression have been proposed; however, none of them reliably predict the progression of the disease and the origin of cardiac abnormalities. Genetic approaches have focused on genes related to the immune response, but few have studied genes associated with cardiac function. Apolipoprotein-A1 (APO-A1) is the main component of high-density lipoproteins, with known cardioprotective effects; polymorphisms in this gene have been associated with coronary diseases. The purpose of this study was to analyze the role of APO-A1 genetic variants in the development of chronic chagasic cardiomyopathy, in patients from the Province of Córdoba.

Blood samples from 91 patients with positive serology for Chagas, from the city of Córdoba (Hospital Nacional de Clínicas, Clínica Sucre and Hospital San Roque) were analyzed. The patients were classified as: G1 (n=49): without cardiac alterations, G2 (n=32): with mild cardiac alterations (electrocardiographic alterations) and G3 (n=10): with severe cardiac alterations (electrocardiographic and echocardiographic alterations). APO-A1 G-75A (rs670) and C+83T (rs5069) polymorphisms were determined by PCR-RFLP. Differences between allelic and genotypic frequencies were analyzed using chi-square/Fisher's exact test and logistic regression.

Both allele and genotypic frequencies for both polymorphisms were similar between the 3 groups studied and were not associated with the development (G1 vs G2+G3) or the progression (G2 vs G3) of cardiomyopathy. Logistic regression analysis showed that exposure to the less frequent allele of each polymorphism was not related to development [OR rs670_A=1.21 (0.67-2.17); OR rs5069_T=0.91 (0.51-1.65)] or with progression [OR rs670_A=1.04 (0.39-2.80); OR rs5069_T=2.14 (0.79-5.77)] of chagasic cardiomyopathy. However, being heterozygous for the rs5069 polymorphism insinuates as a possible predictor for the development of cardiomyopathy (p=0.0787) in relation to being homozygous for the most frequent allele.

The results obtained to date suggest that APO-A1 genetic variants would not have a significant contribution to the development of chronic chagasic cardiomyopathy in the population studied; the inclusion of a larger number of patients is necessary for more conclusive results.