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https://www.arca.fiocruz.br/handle/icict/58544
CANDIDATE GENE ANALYSIS OF OCULAR TOXOPLASMOSIS IN BRAZIL: EVIDENCE FOR A ROLE FOR TOLL-LIKE RECEPTOR 9 (TLR9)
genetic polymorphisms
toll-like receptors
toxoplasmic retinochoroiditis
Brazil
Author
Affilliation
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brasil/Cambridge Institute for Medical Research and Department of Medicine. University of Cambridge School of Clinical Medicine. Cambridge, UK/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil
Cambridge Institute for Medical Research and Department of Medicine. University of Cambridge School of Clinical Medicine. Cambridge, UK
Cambridge Institute for Medical Research and Department of Medicine. University of Cambridge School of Clinical Medicine. Cambridge, UK/Universidade Federal da Bahia. Salvador, BA, Brasil
Cambridge Institute for Medical Research and Department of Medicine. University of Cambridge School of Clinical Medicine. Cambridge, UK/Telethon Institute for Child Health Research. Centre for Child Health Research. The University of Western Australia. Subiaco, Australia
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brasil
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brasil
Telethon Institute for Child Health Research. Centre for Child Health Research. The University of Western Australia. Subiaco, Australia
Cambridge Institute for Medical Research and Department of Medicine. University of Cambridge School of Clinical Medicine. Cambridge, UK
Cambridge Institute for Medical Research and Department of Medicine. University of Cambridge School of Clinical Medicine. Cambridge, UK/Universidade Federal da Bahia. Salvador, BA, Brasil
Cambridge Institute for Medical Research and Department of Medicine. University of Cambridge School of Clinical Medicine. Cambridge, UK/Telethon Institute for Child Health Research. Centre for Child Health Research. The University of Western Australia. Subiaco, Australia
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brasil
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brasil
Telethon Institute for Child Health Research. Centre for Child Health Research. The University of Western Australia. Subiaco, Australia
Abstract
Toxoplasma gondii infection is an important mediator of ocular disease in Brazil more frequently than reported from elsewhere. Infection and pathology are characterized by a strong proinflammatory response which in mice is triggered by interaction of the parasite with the toll-like receptor (TLR)/MyD88 pathway. A powerful way to identify the role of TLRs in humans is to determine whether polymorphisms at these loci influence susceptibility to T. gondii-mediated pathologies. Here we report on a small family-based study (60 families; 68 affected offspring) undertaken in Brazil which was powered for large effect sizes using single nucleotide polymorphisms with minor alleles frequencies > 0.3. Of markers in TLR2, TLR5 and TLR9 that met these criteria, we found an association Family Based Association Tests [(FBAT) Z score = 4.232; p = 1.5 x 10(-5); p(corrected) = 1.2 x 10(-4)] between the C allele (frequency = 0.424; odds ratio = 7; 95% confidence interval 1.6-30.8) of rs352140 at TLR9 and toxoplasmic retinochoroiditis in Brazil. This supports the hypothesis that direct interaction between T. gondii and TLR9 may trigger proinflammatory responses that lead to severe pathologies such as the ocular disease that is associated with this infection in Brazil
Keywords
toxoplasmosisgenetic polymorphisms
toll-like receptors
toxoplasmic retinochoroiditis
Brazil
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