Genetic Polymorphisms of Manganese-Dependent Superoxide Dismutase in Chagas Disease

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Abstract

Background

Infection with Trypanosoma cruzi triggers inflammatory mechanisms and induces the activity of manganese-dependent superoxide dismutase. Genetic single-nucleotide polymorphisms of this enzyme generate proteins with reduced enzymatic activity. The aims of this study were to determine the frequency of the polymorphisms Ala-9Val and Ile58Thr of the manganese-dependent superoxide dismutase gene in DNA from chagasic and nonchagasic patients and to establish a relationship between these polymorphisms with chronic chagasic cardiomyopathy.

Methods

Two hundred fifty-eight unrelated patients underwent a general clinical examination and an electrocardiogram, a chest radiograph, and a 12-lead color Doppler echocardiogram were taken. Besides, we evaluate liver and renal function, lipid profile, and diagnosis of Chagas disease and genetic polymorphisms by polymerase chain reaction–restriction fragment length polymorphism. The patients were classified as nonchagasic group with negative serology for Chagas disease and the chagasic group with positive serology. This group was subdivided into asymptomatic when patients did not present abnormal cardiac symptoms and symptomatic if the chest radiograph, electrocardiogram, and/or color Doppler echocardiogram showed some alteration.

Results

The female chagasic population shows a high frequency of the ile58ile genotype (P = 0.010; odds ratio, 3.3; 95% confidence interval, 1.35–8.38). Lower frequency of the ala-9ala genotype was detected in symptomatic Chagas patients (P = 0.001; odds ratio, 3.147; 95% confidence interval, 1.39–7.482). The analysis revealed an interaction between the ala/ala + val/val genotype (P = 0.0108) with the plasma concentration of low-density lipoprotein cholesterol in the symptomatic Chagas group.

Conclusions

Our results show that the presence of the val allele is associated with chronic chagasic cardiomyopathy. The prognostic value of these results should be more deeply investigated.

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