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

Authors: Farre, L  Bittencourt, AL  Silva-Santos, G  Almeida, A  Silva, AC  Decanine, D  Soares, GM  Alcantara LC, JR  Van Dooren, S  Galvao-Castro, B  Vandamme, AM  Van Weyenbergh, J 
Citation: Farre L, etal., J Leukoc Biol. 2008 Jan;83(1):220-2. Epub 2007 Oct 25.
Pubmed: (View Article at PubMed) PMID:17962369
DOI: Full-text: DOI:10.1189/jlb.0407198

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-gamma-induced but not basal FAS mRNA levels were increased significantly (P=0.049) in PBMCs from AA versus GG individuals, demonstrating the IFN-dependent 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.

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RGD Object Information
RGD ID: 11049147
Created: 2016-04-05
Species: All species
Last Modified: 2016-04-05
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.