| Author | Alcaïs, Alexandre | |
| Author | Alter, Andrea | |
| Author | Antoni, Guillemette | |
| Author | Orlova, Marianna | |
| Author | Thuc, Nguyen Van | |
| Author | Singh, Meenakshi | |
| Author | Vanderborght, Patrícia Rosa | |
| Author | Katoch, Kiran | |
| Author | Mira, Marcelo Távora | |
| Author | Thai, Vu Hong | |
| Author | Huong, Ngyuen Thu | |
| Author | Ba, Nguyen Ngoc | |
| Author | Moraes, Milton Ozório | |
| Author | Mehra, Narinder | |
| Author | Schurr, Erwin | |
| Author | Abel, Laurent | |
| Access date | 2024-09-02T14:26:10Z | |
| Available date | 2024-09-02T14:26:10Z | |
| Document date | 2007 | |
| Citation | ALCAÏS, Alexandre et al. Stepwise replication identifies a low-producing lymphotoxin-α allele as a major risk factor for early-onset leprosy. Nature Genetics, v. 39, n. 4, p. 517-522, Apr. 2007. | |
| ISSN | 1546-1718 | |
| URI | https://www.arca.fiocruz.br/handle/icict/65699 | |
| Description | Produção científica do Laboratório de Hanseníase. | pt_BR |
| Language | eng | en_US |
| Publisher | Nature Research | |
| Rights | restricted access | |
| Title | Stepwise replication identifies a low-producing lymphotoxin-α allele as a major risk factor for early-onset leprosy | en_US |
| Type | Article | |
| DOI | 10.1038/ng2000 | |
| Abstract | Host genetics has an important role in leprosy, and variants in the shared promoter region of PARK2 and PACRG were the first major susceptibility factors identified by positional cloning1,2. Here we report the linkage disequilibrium mapping of the second linkage peak of our previous genome-wide scan1, located close to the HLA complex. In both a Vietnamese familial sample and an Indian case-control sample, the low-producing lymphotoxin-α (LTA)+80 A allele was significantly associated with an increase in leprosy risk (P = 0.007 and P = 0.01, respectively). Analysis of an additional case-control sample from Brazil and an additional familial sample from Vietnam showed that the LTA+80 effect was much stronger in young individuals. In the combined sample of 298 Vietnamese familial trios, the odds ratio of leprosy for LTA+80 AA/AC versus CC subjects was 2.11 (P = 0.000024), which increased to 5.63 (P = 0.0000004) in the subsample of 121 trios of affected individuals diagnosed before 16 years of age. In addition to identifying LTA as a major gene associated with early-onset leprosy, our study highlights the critical role of case- and population-specific factors in the dissection of susceptibility variants in complex diseases. | en_US |
| Affilliation | Institut National de la Santé et de la Recherche Médicale. Laboratoire de Génétique Humaine des Maladies Infectieuses. Paris, France / Université Paris René Descartes. Faculté Médecine Necker. Paris, France. | |
| Affilliation | McGill University. McGill Centre for the Study of Host Resistance. Department of Human Genetics. Montreal, QC, Canada / McGill University. McGill Centre for the Study of Host Resistance. Department of Medicine. Montreal, QC, Canada / McGill University. McGill Centre for the Study of Host Resistance. Department of Biochemistry. Montreal, QC, Canada. | |
| Affilliation | Institut National de la Santé et de la Recherche Médicale. Laboratoire de Génétique Humaine des Maladies Infectieuses. Paris, France. | |
| Affilliation | McGill University. McGill Centre for the Study of Host Resistance. Department of Human Genetics. Montreal, QC, Canada / McGill University. McGill Centre for the Study of Host Resistance. Department of Medicine. Montreal, QC, Canada / McGill University. McGill Centre for the Study of Host Resistance. Department of Biochemistry. Montreal, QC, Canada. | |
| Affilliation | Hospital for Dermato-Venereology. Ho Chi Minh City, Vietnam. | |
| Affilliation | All-India Institute of Medical Sciences. Department of Transplant Immunology and Immunogenetics. New Delhi, India. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Medicina Tropical. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Central JALMA Institute of Leprosy and Other Infectious Diseases. Taj Ganj, Agra, India. | |
| Affilliation | Pontifícia Universidade Católica do Paraná. Centro de Ciências Biológicas e da Saúde. Curitiba, PR, Brasil. | |
| Affilliation | Hospital for Dermato-Venereology. Ho Chi Minh City, Vietnam. | |
| Affilliation | Hospital for Dermato-Venereology. Ho Chi Minh City, Vietnam. | |
| Affilliation | Hospital for Dermato-Venereology. Ho Chi Minh City, Vietnam. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Medicina Tropical. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | All-India Institute of Medical Sciences. Department of Transplant Immunology and Immunogenetics. New Delhi, India. | |
| Affilliation | McGill University. McGill Centre for the Study of Host Resistance. Department of Human Genetics. Montreal, QC, Canada / McGill University. McGill Centre for the Study of Host Resistance. Department of Medicine. Montreal, QC, Canada / McGill University. McGill Centre for the Study of Host Resistance. Department of Biochemistry. Montreal, QC, Canada. | |
| Affilliation | Institut National de la Santé et de la Recherche Médicale. Laboratoire de Génétique Humaine des Maladies Infectieuses. Paris, France / Université Paris René Descartes. Faculté Médecine Necker. Paris, France. | |
| Subject | Lymphotoxin-alpha (LTA) | en_US |
| Subject | Leprosy susceptibility | en_US |
| Subject | Genetic association | en_US |
| Subject | HLA region | en_US |
| e-ISSN | 1061-4036 | |
