Tumor necrosis factor (TNF) is a potent proinflammatory cytokine involved i
n asthma and atopy. Increased TNF-cu levels have been found in airway biops
ies and bronchoalveolar lavage fluids from asthmatic patients. Constitution
al variations in the TNF-alpha secretion levels in vitro are associated wit
h molecular polymorphisms located within and around the TNF loci. Our study
objective was to investigate the association between atopy and two describ
ed di-allelic polymorphisms in the TNF locus: a G to A transition at positi
on -308 in the 5'-promoter region of the TNFA gene (TNFA*1 and TNFA*2 allel
es) and an NcoI restriction fragment length polymorphism (RFLP) in the firs
t intron of the TNFB gene (TNFB*1 and TNFB*2 alleles). The genetic study wa
s performed in 65 unrelated atopic patients and 60 healthy controls. The re
gions of interest were amplified from genomic DNA using specific primers an
d polymerase chain reaction. SSP-PCR analysis for TNFA -308 polymorphism ge
notyping and endonuclease digestion analysis for the TNFB NcoI RFLP were us
ed. The frequency of the TNFA*2 allele was significantly higher in atopic s
ubjects compared to the control group (38.5% vs. 10.5%; chi(2) = 32.06; p <
0.0001). The TNFA*2 allele is associated with a higher risk for the develop
ment of atopy (risk ratio = 9.44; EF = 0.65; chi(2) = 30.06 p <0.0005). On
the other hand, no significant association between the TNFB alleles and ato
py was found. In conclusion, the TNFA*2 allele could be also a genetic risk
marker for the predisposition to atopy in our population, as has been repo
rted in other studies. Either the TNFA gene itself or a linked gene on chro
mosome region 6p21, which has yet to be identified, is a candidate gene for
susceptibility to atopy.