Functional IL18 polymorphism and susceptibility to Chronic Chagas Disease

Cytokine. 2015 May;73(1):79-83. doi: 10.1016/j.cyto.2015.01.037. Epub 2015 Mar 2.

Abstract

Background: Chronic 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 results: We 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.

Conclusions: Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome.

Keywords: Cardiomyopathy; Chagas; IL18; Severity; polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Chagas Cardiomyopathy / genetics*
  • Chagas Cardiomyopathy / physiopathology
  • Chronic Disease
  • Cohort Studies
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Interleukin-18 / genetics*
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Stroke Volume

Substances

  • Interleukin-18