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

• Published in: PLoS neglected tropical diseases Vol. 13; no. 11; p. e0007859
• Main Authors: Strauss, Mariana, Acosta-Herrera, Marialbert, Alcaraz, Alexia, Casares-Marfil, Desiré, Bosch-Nicolau, Pau, Lo Presti, María Silvina, Molina, Israel, González, Clara Isabel, Martín, Javier
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-11-2019; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Antigens; Argentina; Biology and Life Sciences; Bolivia; Brazil; Cardiomyopathy; Chagas disease; Chagas Disease - genetics; Chagas Disease - parasitology; Chronic infection; Cohort Studies; Cohorts; Colombia; Comparative analysis; Cytokines; Development and progression; Disease susceptibility; Diseases; Female; Genetic analysis; Genetic aspects; Genetic diversity; Genetic factors; Genetic polymorphisms; Genetic Predisposition to Disease; Genetic variance; Genomes; Hispanic Americans - genetics; Hospitals; Humans; Infection; Infections; Interleukin 1; Interleukin 18; Interleukin-18 - genetics; Interleukins; Latin America; Male; Medical research; Medicine and Health Sciences; Middle Aged; Myocardial diseases; Parasitic diseases; People and places; Physical Sciences; Polymorphism, Single Nucleotide; Population genetics; Population studies; Populations; Research and Analysis Methods; Sex; Studies; Testing; Tropical diseases; Trypanosoma cruzi - physiology; Tumor necrosis factor-TNF; Vector-borne diseases; Young Adult; Brazil; Colombia; Argentina; Bolivia; Latin America; Spain
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0007859

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.