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

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 pr...

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Bibliographic Details
Published in:PLoS neglected tropical diseases 2019-11, Vol.13 (11), p.e0007859-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: Article
Language:English
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
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Description
Summary: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.
ISSN:1935-2735
1935-2727
1935-2735
DOI:10.1371/journal.pntd.0007859