Desiré Casares-Marfil1, Mariana Strauss2, Pau Bosch-Nicolau3, María Silvina Lo Presti2, Israel Molina3, Christophe Chevillard4, Edecio Cunha-Neto5, Ester Sabino6, Antonio Luiz P Ribeiro7,8, Clara Isabel González9, Javier Martín1, Marialbert Acosta-Herrera1. 1. Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain. 2. Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, FCM, INICSA-CONICET-UNC, Córdoba, Argentina. 3. Unidad de Medicina Tropical y Salud Internacional Hospital Universitari Vall d'Hebron, PROSICS, Barcelona, Spain. 4. INSERM, Aix Marseille university, TAGC, UMR_1090, Marseille, France. 5. Laboratory of Immunology, Heart Institute (InCor)/Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. 6. Instituto de Medicina Tropical Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. 7. Centro de Telessaúde, Hospital das Clínicas, Belo Horizonte, Brazil. 8. Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. 9. Grupo de Inmunología y Epidemiología Molecular, Escuela de Microbiología, Universidad Industrial de Santander, Bucaramanga, Colombia.
Abstract
BACKGROUND: Chagas disease is an infectious disease caused by the parasite Trypanosoma cruzi and is endemic from Latin American countries. The goal of our study was to identify novel genetic loci associated with chronic Chagas cardiomyopathy development in Chagas disease patients from different Latin American populations. METHODS: We performed a cross-sectional, nested case-control study including 3 sample collections from Colombia, Argentina, and Bolivia. Samples were genotyped to conduct a genome-wide association study (GWAS). These results were meta-analyzed with summary statistic data from Brazil, gathering a total of 3413 Chagas disease patients. To identify the functional impact of the associated variant and its proxies, we performed an in silico analysis of this region. RESULTS: The meta-analysis revealed a novel genome-wide statistically significant association with chronic Chagas cardiomyopathy development in rs2458298 (OR = 0.90, 95%CI = 0.87-0.94, P-value = 3.27 × 10-08), nearby the SAC3D1 gene. In addition, further in silico analyses displayed functional relationships between the associated variant and the SNX15, BAFT2, and FERMT3 genes, related to cardiovascular traits. CONCLUSIONS: Our findings support the role of the host genetic factors in the susceptibility to the development of the chronic cardiac form of this neglected disease.
BACKGROUND: Chagas disease is an infectious disease caused by the parasite Trypanosoma cruzi and is endemic from Latin American countries. The goal of our study was to identify novel genetic loci associated with chronic Chagas cardiomyopathy development in Chagas disease patients from different Latin American populations. METHODS: We performed a cross-sectional, nested case-control study including 3 sample collections from Colombia, Argentina, and Bolivia. Samples were genotyped to conduct a genome-wide association study (GWAS). These results were meta-analyzed with summary statistic data from Brazil, gathering a total of 3413 Chagas disease patients. To identify the functional impact of the associated variant and its proxies, we performed an in silico analysis of this region. RESULTS: The meta-analysis revealed a novel genome-wide statistically significant association with chronic Chagas cardiomyopathy development in rs2458298 (OR = 0.90, 95%CI = 0.87-0.94, P-value = 3.27 × 10-08), nearby the SAC3D1 gene. In addition, further in silico analyses displayed functional relationships between the associated variant and the SNX15, BAFT2, and FERMT3 genes, related to cardiovascular traits. CONCLUSIONS: Our findings support the role of the host genetic factors in the susceptibility to the development of the chronic cardiac form of this neglected disease.
Authors: Pau Bosch-Nicolau; Juan Espinosa-Pereiro; Fernando Salvador; Adrián Sánchez-Montalvá; Israel Molina Journal: Front Cardiovasc Med Date: 2022-01-31
Authors: Ester Cerdeira Sabino; Lucas Augusto Moysés Franco; Gabriela Venturini; Mariliza Velho Rodrigues; Emanuelle Marques; Lea Campos de Oliveira-da Silva; Larissa Natany Almeida Martins; Ariela Mota Ferreira; Paulo Emílio Clementino Almeida; Felipe Dias Da Silva; Sâmara Fernandes Leite; Maria do Carmo Pereira Nunes; Desiree Sant'Ana Haikal; Claudia Di Lorenzo Oliveira; Clareci Silva Cardoso; Jonathan G Seidman; Christine E Seidman; Juan P Casas; Antonio Luiz Pinho Ribeiro; Jose E Krieger; Alexandre C Pereira Journal: PLoS Negl Trop Dis Date: 2022-10-10
Authors: Desiré Casares-Marfil; Beatriz Guillen-Guio; Jose M Lorenzo-Salazar; Héctor Rodríguez-Pérez; Martin Kerick; Mayra A Jaimes-Campos; Martha L Díaz; Elkyn Estupiñán; Luis E Echeverría; Clara I González; Javier Martín; Carlos Flores; Marialbert Acosta-Herrera Journal: Hum Mol Genet Date: 2021-11-30 Impact factor: 6.150