1. Association of IL18 genetic polymorphisms with Chagas disease in Latin American populations
- Author
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Strauss, Mariana, Acosta Herrera, Marialbert, Alcaraz, Alexia, Casares Marfil, Desiré, Bosch Nicolau, Pau, Lo Presti, Maria Silvina, Molina, Israel, González, Clara Isabel, Martín, Javier, Chagas Genetics CYTED Network, Universidad Nacional de Córdoba (Argentina), Ministerio de Ciencia y Tecnología de Córdoba (Argentina), Institut Català de la Salut, [Strauss M, Lo Presti MS] Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, FCM, INICSA-CONICET-UNC, Córdoba, Argentina. [Acosta-Herrera M, Alcaraz A, Casares-Marfil D] Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, PTS Granada, Granada, España. [Bosch-Nicolau P, Molina I] Unitat de Medicina Tropical i Salut Internacional Drassanes, Vall d'Hebron Hospital Universitari, Barcelona, Spain. PROSICS, Barcelona, España, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
0301 basic medicine ,Male ,RC955-962 ,enfermedades parasitarias::infecciones por protozoos::infecciones por Euglenozoa::tripanosomiasis::enfermedad de Chagas [ENFERMEDADES] ,Cohort Studies ,0302 clinical medicine ,Mathematical and Statistical Techniques ,Arctic medicine. Tropical medicine ,Medicine and Health Sciences ,Ethnicities ,Protozoans ,Trypanosoma Cruzi ,education.field_of_study ,Statistics ,Interleukin-18 ,Eukaryota ,Eukaryota::Euglenozoa::Kinetoplastida::Trypanosomatina::Trypanosoma::Trypanosoma cruzi [ORGANISMS] ,purl.org/becyt/ford/3.1 [https] ,Hispanic or Latino ,Middle Aged ,Metaanalysis ,Population groupings ,META-ANALYSIS ,Malalties parasitàries ,Infectious Diseases ,Cohort ,Physical Sciences ,Amèrica Llatina ,purl.org/becyt/ford/3 [https] ,Female ,Public aspects of medicine ,RA1-1270 ,Cardiomyopathies ,Parasitic Diseases::Protozoan Infections::Euglenozoa Infections::Trypanosomiasis::Chagas Disease [DISEASES] ,Brazil ,Cohort study ,Research Article ,Neglected Tropical Diseases ,Chagas disease ,Adult ,Bolivia ,Trypanosoma ,Chagas, Malaltia de ,Geographic Locations::Americas::Latin America [GEOGRAPHICALS] ,030231 tropical medicine ,Population ,Argentina ,Cardiology ,Single-nucleotide polymorphism ,Biology ,Colombia ,Research and Analysis Methods ,Genetic Predisposition ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,purl.org/becyt/ford/3.3 [https] ,Young Adult ,TRYPANOSOMA CRUZI INFECTION ,Genetic variation ,parasitic diseases ,Eukaryota::Euglenozoa::Kinetoplastida::Trypanosomatina::Trypanosoma::Trypanosoma cruzi [ORGANISMOS] ,medicine ,Genetic predisposition ,Parasitic Diseases ,Genetics ,Humans ,Chagas Disease ,Genetic Predisposition to Disease ,Allele ,Statistical Methods ,education ,Aged ,Evolutionary Biology ,CARDIOMYOPATHY ,Protozoan Infections ,Population Biology ,CHAGAS DISEASE ,Public Health, Environmental and Occupational Health ,IL18 ,Organisms ,Biology and Life Sciences ,Latin American people ,medicine.disease ,Tropical Diseases ,Parasitic Protozoans ,030104 developmental biology ,Latin America ,Genetics of Disease ,People and places ,localizaciones geográficas::Américas::Latinoamérica [DENOMINACIONES GEOGRÁFICAS] ,Mathematics ,Population Genetics ,Demography - Abstract
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., This research was supported by grants from Ministerio de Ciencia y Tecnología de Córdoba (GRFT 2017, https://mincyt.cba.gov.ar/), Secretaría de Ciencia y Tecnología, Universidad Nacional de Córdoba, Argentina (https://www.unc.edu.ar/ciencia-y-tecnología/) and Red Iberoamericana de medicina genómica en enfermedad de Chagas - CYTED (http://www.cyted.org). Mariana Strauss performed the experimental work in this article during an internship at the Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Granada, España. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Published
- 2019