Functional IL18 polymorphism and susceptibility to Chronic Chagas Disease

• We have recruited a cohort of Chagas patients (849) + asymptomatic subjects (202).
• We genotyped the rs2043055 marker, located in the IL18 gene, on this cohort.
• We found a significant difference among moderate and severe CCC patients.
• The IL18 rs2043055A/G genotype is more frequent moderate CCC subjects group.
• IL18 rs2043055 may contribute to modulating the Chagas cardiomyopathy outcome.

BackgroundChronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the rest of the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described. IL-18 could potentially amplify the process by inducing increased expression of IFN-γ which in turn can increase the production of IL-18, thereby creating a positive feedback mechanism. In order to assess the contribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the association between a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developing Chagas cardiomyopathy.Methods and resultsWe analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas disease cardiomyopathy patients (n = 849) and asymptomatic subjects (n = 202). We found a significant difference in genotype frequencies among moderate and severe CCC patients with ventricular dysfunction.ConclusionsOur analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome.