Association of IL18 genetic polymorphisms with Chagas disease in Latin American populations

Author summary Chagas disease is a parasitic infection caused by the protozoon Trypanosoma cruzi, is the third most common parasitic infection worldwide, the most important in Latin America and is an emerging disease in non-endemic countries. Actually, millions of people live in areas of exposure and are at risk of contracting the infection. Most of the infected individuals remain asymptomatic for all of their lives, but around 30% of the chronically infected individuals develop irreversible cardiac damage and 10% digestive lesions. Host genetic factors have been suggested to play an important role in the susceptibility or resistance to Chagas disease. In this work, we investigated variants of the IL18 gene in different Latin America populations. This gene encoded the interleukin-18, which is involved in the immune response to intracellular pathogens like T. cruzi. Our results showed that an IL18 gene variant plays an important role in the protection against T. cruzi infection. Host genetic factors have been suggested to play an important role in the susceptibility to Chagas disease. Given the influence of interleukin 18 (IL-18) in the development of the disease, in the present study, we analyzed three IL18 genetic variants (rs2043055, rs1946518, rs360719) regarding the predisposition to Trypanosoma cruzi infection and the development of chronic Chagas cardiomyopathy (CCC), in different Latin America populations. Genetic data of 3,608 patients from Colombia, Bolivia, Argentina, and Brazil were meta-analyzed to validate previous findings with increased statistical power. Seropositive and seronegative individuals were compared for T. cruzi infection susceptibility. In the Colombian cohort, the allelic frequencies of the three variants showed a significant association, with adjustment for sex and age, and also after applying multiple testing adjustments. Among the Colombian and Argentinean cohorts, rs360719 showed a significant genetic effect in a fixed-effects meta-analysis after a Bonferroni correction (OR: 0.76, CI: 0.66-0.89, P = 0.001). For CCC, the rs2043055 showed an association with protection from cardiomyopathy in the Colombian cohort (OR: 0.79, CI: 0.64-0.99, P = 0.037), with adjustment for sex and age, and after applying multiple testing adjustments. The meta-analysis of the CCC vs. asymptomatic patients from the four cohorts showed no evidence of association. In conclusion, our results validated the association found previously in the Colombian cohort suggesting that IL18 rs360719 plays an important role in the susceptibility to T. cruzi infection and no evidence of association was found between the IL18 genetic variants and CCC in the Latin American population studied.