Title: Fas 670 promoter polymorphism is associated to susceptibility, clinical presentation, and survival in adult T cell leukemia
Authors: Farre, L ×
Bittencourt, A L
Silva-Santos, G
Almeida, A
Silva, A C
Decanine, D
Soares, G M
Alcantara, L C
Van Dooren, Sonia
Galvão-Castro, B
Vandamme, Anne-Mieke
Van Weyenbergh, Johan #
Issue Date: Jan-2008
Publisher: Liss
Series Title: Journal of Leukocyte Biology vol:83 issue:1 pages:220-222
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 over-represented significantly 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 associated significantly to susceptibility, clinical manifestation, and survival in ATL.
ISSN: 0741-5400
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Clinical and Epidemiological Virology (Rega Institute)
× corresponding author
# (joint) last author

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