Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/8115
Title: Fas 670 promoter polymorphism is associated to susceptibility, clinical presentation, and survival in adult T cell leukemia.
Authors: Vallve, Maria de Lourdes Farre
Bittencourt, Achilea Candida Lisboa
Santos, Gilvanéia Silva
Almeida, A.
Silva, A. C.
Decanine, Daniele
Soares, G. M.
Alcantara, Luiz Carlos Júnior
Van Dooren, Sonia
Castro Filho, Bernardo Galvão
Vandamme, Anne-Mieke
Van Weyenbergh, Johan Jozef Rosa Maria
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Imunorregulação e Microbiologia. Salvador, BA, Brasil
Hospital Universitário Professor Edgard Santos. HUPES. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Imunorregulação e Microbiologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Imunorregulação e Microbiologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Imunorregulação e Microbiologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Imunorregulação e Microbiologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Imunorregulação e Microbiologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil
Rega Institute. Clinical and Epidemiological Virology. Leuven, Belgium
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil
Rega Institute. Clinical and Epidemiological Virology. Leuven, Belgium
Instituto de Investigação em Imunologia. iii–Millenium Institute. São Paulo, SP, Brasil
Abstract: Fas (TNFRSF6/Apo-1/CD95) is a type I transmembrane receptor, which mediates apoptosis. Fas gene mutations, aberrant transcripts, and abundant expression of Fas have been reported in adult T cell leukemia (ATL). To further elucidate the role of Fas in ATL pathogenesis, we investigated whether the –670 FAS promoter A/G polymorphism (STAT1- binding site) might contribute to susceptibility and clinical outcome in ATL. Thirty-one patients with ATL, 33 healthy, human T lymphotropic virus type 1-infected individuals, and 70 healthy, uninfected controls were genotyped for the FAS –670 polymorphism by PCR-restriction fragment-length polymorphism. The AA genotype was significantly over-represented in ATL patients in comparison with healthy controls (P 0.006), as well as asymptomatics (P 0.037), corresponding to an odds ratio (OR) of 3.79 [95% confidence intervals (CI; 1.28–11.41)] and 4.58 [95% CI (1.13–20.03)], respectively. The AA group also comprised significantly more aggressive (acute and lymphoma) clinical subtypes [P 0.012; OR 8.40; 95% CI (1.60–44.12)]. In addition, we observed a statistically significant association between GG genotype and survival (log rank test, P 0.032). Finally, IFN- -induced but not basal FAS mRNA levels were increased significantly (P 0.049) in PBMCs from AA versus GG individuals, demonstrating the IFNdependent functionality of the –670 polymorphism. In conclusion, our results demonstrate that a functional Fas promoter polymorphism is significantly associated to susceptibility, clinical manifestation, and survival in ATL.
Keywords: TNFRSF6
ATL
STAT1
HTLV-1
Apoptosis
DeCS: Antígenos CD95/genética
Predisposição Genética para Doença/genética
Leucemia de Células T/genética
Polimorfismo de Nucleotídeo Único/genética
Regiões Promotoras Genéticas/genética
Antígenos CD95/imunologia
Seguimentos
Genótipo
Infecções por HTLV-I/imunologia
Humanos
Interferon gama/farmacologia
Leucemia de Células T/diagnóstico
Leucócitos Mononucleares/efeitos de drogas
RNA Mensageiro/genética
Fatores de Risco
Taxa de Sobrevida
Issue Date: 2007
Publisher: Society for Leukocyte Biology
Citation: VALLVE, M. L. F. et al. Fas 670 promoter polymorphism is associated to susceptibility, clinical presentation, and survival in adult T cell leukemia. Journal of Leukocyte Biology, v. 83, n. 1, p. 220-222, 2008.
DOI: 10.1189/jlb.0407198
ISSN: 0741-5400
Copyright: restricted access
Appears in Collections:BA - IGM - Artigos de Periódicos

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