A Specific Polymorphic Genotype Modulates the Risk of Parasitemia While , , and Variant Profiles and HIV Infection Protect Against Cardiomyopathy in Chagas Disease.

BACKGROUND

Chagas disease caused by () affects approximately six million individuals worldwide. Clinical manifestations are expected to occur due to the parasite persistence and host immune response. Herein we investigated potential associations between , , , or polymorphism profiles and cardiomyopathy or parasitemia, as well as the impact of HIV infection on cardiopathy.

METHODS

Two hundred twenty-six patients and 90 control individuals were analyzed. rs1143627 T>C, rs1800795 C>G, rs2275913 G>A, rs187238 C>G, and rs1946518 C>A SNVs were analyzed by real-time PCR and parasitemia by PCR.

RESULTS

Our data revealed association between a cytokine gene polymorphism and parasitemia never previously reported. The rs1800795 CG genotype lowered the risk of positive parasitemia (OR = 0.45, 95% CI 0.24-0.86, P = 0.015). Original findings included associations between rs2275913 AA and s1946518 AA genotypes with decreased risk of developing cardiomyopathy (OR = 0.27, 95% CI 0.07-0.97, P = 0.044; and OR = 0.35, 95% CI 0.14-0.87, P = 0.023, respectively). rs1946518 AA and rs1143627 TC were associated with reduced risk for cardiomyopathy severity, including NYHA (New York Heart Association) class ≥ 2 (OR = 0.21, 95% CI 0.06-0.68, P = 0.009; and OR = 0.48, 95% CI 0.24-0.95, P = 0.036, respectively) and LVEF (left ventricular ejection fraction) <45% for rs1946518 AA (OR = 0.22, 95% CI 0.05-0.89, P = 0.034). A novel, unexpected protective effect of HIV infection against development/progression of cardiomyopathy was identified, based on a lower risk of developing cardiopathy (OR = 0.48, 95% CI 0.23-0.96, P = 0.039), NYHA class ≥ 2 (OR = 0.15, 95% CI 0.06-0.39, P < 0.001), and LVEF < 45% (OR = 0.03, 95% CI 0.00-0.25, P = 0.001). Digestive involvement was negatively associated with NYHA ≥ 2 and LVEF < 45% (OR = 0.20, 95% CI 0.09-0.47, P < 0.001; and OR = 0.24, 95% CI 0.09-0.62, P = 0.004, respectively).

CONCLUSIONS

Our data support a protective role of AA, AA, and TC genotypes against development/progression of cardiomyopathy and a modulatory effect of the CG genotype on the risk of parasitemia in Chagas disease. Notably, HIV infection was shown to protect against development/progression of cardiopathy, potentially associated with a synergistic effect of HIV and highly active antiretroviral therapy (HAART), attenuating a Th1-mediated response in the myocardium. This proposed hypothesis requires confirmation, however, in larger and more comprehensive future studies.