Increased TNFA*2, but not TNFB*1, allele frequency in Spanish atopic patients

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.