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

Tumor necrosis factor (TNF) is a potent proinflammatory cytokine involved in asthma and atopy. Increased TNF-alpha levels have been found in airway biopsies and bronchoalveolar lavage fluids from asthmatic patients. Constitutional variations in the TNF-alpha secretion levels in vitro are associated with molecular polymorphisms located within and around the TNF loci. Our study objective was to investigate the association between atopy and two described di-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'-promoter region of the TNFA gene (TNFA*1 and TNFA*2 alleles) and an Ncol restriction fragment length polymorphism (RFLP) in the first intron of the TNFB gene (TNFB*1 and TNFB*2 alleles). The genetic study was performed in 65 unrelated atopic patients and 60 healthy controls. The regions of interest were amplified from genomic DNA using specific primers and polymerase chain reaction. SSP-PCR analysis for TNFA -308 polymorphism genotyping and endonuclease digestion analysis for the TNFB Ncol RFLP were used. The frequency of the TNFA*2 allele was significantly higher in atopic subjects compared to the control group (38.5% vs. 10.5%; chi2 = 32.06; p <0.0001). The TNFA*2 allele is associated with a higher risk for the development of atopy (risk ratio = 9.44; EF = 0.65; chi2 = 30.06 p <0.0005). On the other hand, no significant association between the TNFB alleles and atopy 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 reported in other studies. Either the TNFA gene itself or a linked gene on chromosome region 6p21, which has yet to be identified, is a candidate gene for susceptibility to atopy.