Fas 670 promoter polymorphism is associated to susceptibility, clinical presentation, and survival in adult T cell leukemia.

dc.creatorVallve, Maria de Lourdes Farre
dc.creatorBittencourt, Achilea Candida Lisboa
dc.creatorSantos, Gilvanéia Silva
dc.creatorAlmeida, A.
dc.creatorSilva, A. C.
dc.creatorDecanine, Daniele
dc.creatorSoares, G. M.
dc.creatorAlcantara, Luiz Carlos Júnior
dc.creatorVan Dooren, Sonia
dc.creatorCastro Filho, Bernardo Galvão
dc.creatorVandamme, Anne-Mieke
dc.creatorVan Weyenbergh, Johan Jozef Rosa Maria
dc.date2014-08-01T15:59:01Z
dc.date2014-08-01T15:59:01Z
dc.date2007
dc.date.accessioned2023-09-26T23:45:21Z
dc.date.available2023-09-26T23:45:21Z
dc.identifierVALLVE, 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.
dc.identifier0741-5400
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/8115
dc.identifier10.1189/jlb.0407198
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8893874
dc.descriptionFas (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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherSociety for Leukocyte Biology
dc.rightsrestricted access
dc.subjectTNFRSF6
dc.subjectATL
dc.subjectSTAT1
dc.subjectHTLV-1
dc.subjectApoptosis
dc.subjectAntígenos CD95/genética
dc.subjectPredisposição Genética para Doença/genética
dc.subjectLeucemia de Células T/genética
dc.subjectPolimorfismo de Nucleotídeo Único/genética
dc.subjectRegiões Promotoras Genéticas/genética
dc.subjectAntígenos CD95/imunologia
dc.subjectSeguimentos
dc.subjectGenótipo
dc.subjectInfecções por HTLV-I/imunologia
dc.subjectHumanos
dc.subjectInterferon gama/farmacologia
dc.subjectLeucemia de Células T/diagnóstico
dc.subjectLeucócitos Mononucleares/efeitos de drogas
dc.subjectRNA Mensageiro/genética
dc.subjectFatores de Risco
dc.subjectTaxa de Sobrevida
dc.titleFas 670 promoter polymorphism is associated to susceptibility, clinical presentation, and survival in adult T cell leukemia.
dc.typeArticle


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