Fas 670 promoter polymorphism is associated to susceptibility, clinical presentation, and survival in adult T cell leukemia.
2008
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.
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