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Autor | Fava, Vinicius M. | |
Autor | Marques, Carolinne Sales | |
Autor | Alcaïs, Alexandre | |
Autor | Moraes, Milton O. | |
Autor | Schurr, Erwin | |
Fecha de acceso | 2018-02-08T13:33:07Z | |
Fecha de disponibilización | 2018-02-08T13:33:07Z | |
Fecha de publicación | 2017 | |
Referencia | FAVA, Vinicius M. et al. Age-Dependent Association of TNFSF15/TNFSF8 Variants and Leprosy Type 1 Reaction. . Frontiers in Immunology, v.8, Article 155, 7p, Feb. 2017. | pt_BR |
ISSN | 1664-3224 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/24774 | |
Idioma | eng | pt_BR |
Editor | Frontiers Media | pt_BR |
Derechos de autor | open access | pt_BR |
Palabras clave en Portugués | Hanseníase | pt_BR |
Palabras clave en Portugués | Doença de Crohn | pt_BR |
Palabras clave en Portugués | idade no diagnóstico de doença | pt_BR |
Palabras clave en Portugués | estudos de associação | pt_BR |
Palabras clave en Portugués | resposta inflamatória excessiva | pt_BR |
Palabras clave en Portugués | reação de tipo 1 | pt_BR |
Título | Age-Dependent Association of TNFSF15/TNFSF8 Variants and Leprosy Type 1 Reaction | pt_BR |
Tipo del documento | Article | pt_BR |
DOI | 10.3389/fimmu.2017.00155 | |
Resumen en Inglés | A current major challenge in leprosy control is the prevention of permanent disabilities. Host pathological inflammatory responses termed type 1 reaction (T1R) are a leading cause of nerve damage for leprosy patients. The environmental or inherited factors that predispose leprosy cases to undergo T1R are not known. However, studies have shown an important contribution of host genetics for susceptibility to T1R. We have previously identified variants encompassing the TNFSF15/TNFSF8 genes as T1R risk factors in a Vietnamese sample and replicated this association in a Brazilian sample. However, we failed to validate in Brazilian patients the strong association of TNFSF15/TNFSF8 markers rs6478108 and rs7863183 with T1R that we had observed in Vietnamese patients. Here, we investigated if the lack of validation of these variants was due to age-dependent effects on association using four independent population samples, two from Brazil and two from Vietnam. In the combined analysis across the four samples, we observed a strong association of the TNFSF15/TNFSF8 variants rs6478108, rs7863183, and rs3181348 with T1R (pcombined = 1.5E-05, pcombined = 1.8E-05, and pcombined = 6.5E-06, respectively). However, the association of rs6478108 with T1R was more pronounced in leprosy cases under 30 years of age compared to the global sample [odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.54-2.46, pcombined = 2.5E-08 versus OR = 1.46, 95% CI = 1.23-1.73, pcombined = 1.5E-05]. A multivariable analysis indicated that the association of rs6478108 with T1R was independent of either rs7863183 or rs3181348. These three variants are known regulators of the TNFSF8 gene transcription level in multiple tissues. The age dependency of association of rs6478108 and T1R suggests that the genetic control of gene expression varies across the human life span. | pt_BR |
Afiliación | Research Institute of the McGill University Health Centre. Program in Infectious Diseases and Immunity in Global Health. Montreal, Quebec, canada / McGill University. The McGill International TB Centre, Departments of Human Genetics and Medicine. Montreal, Quebec, Canada. | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil. | pt_BR |
Afiliación | Institut National de la Santé et de la Recherche Médicale. Laboratory of Human Genetics of Infectious Diseases. Necker Branch. Paris, France / University Paris Descartes. Imagine Institute. Paris, France / Rockefeller University. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. New York, USA. | pt_BR |
Afiliación | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil. | pt_BR |
Afiliación | Research Institute of the McGill University Health Centre. Program in Infectious Diseases and Immunity in Global Health. Montreal, Quebec, canada / McGill University. The McGill International TB Centre, Departments of Human Genetics and Medicine. Montreal, Quebec, Canada / McGill University. Deparment of Medicine. Montreal, QC, Canada. | pt_BR |
Palavras clave en Inglês | age at disease diagnosis | pt_BR |
Palavras clave en Inglês | excessive inflammatory response | pt_BR |
Palavras clave en Inglês | leprosy | pt_BR |
Palavras clave en Inglês | TNFSF8 | pt_BR |
Palavras clave en Inglês | TNFSF15 | pt_BR |
Palavras clave en Inglês | type 1 reaction | pt_BR |
Palavras clave en Inglês | association studies | pt_BR |
Palavras clave en Inglês | Crohn’s disease | pt_BR |
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