POLYMORPHISM IN TRANSPORTER ANTIGEN PEPTIDES GENE (TAP1) ASSOCIATED WITH ATOPY IN TUNISIANS

Background: Transporter antigen peptide 1 (TAP1) and TAP2 gene product s form a transporter molecule involved in antigen presentation. Polymo rphic residues have been described in both genes and could have functi onal consequences in the immune response. Objective: We designed a cas e-control study to investigate the potential association of polymorphi sm of the TAP1 gene with atopy. Methods: We used the amplification ref ractory mutation system polymerase chain reaction to characterize TAP1 gene polymorphism in 84 unrelated Tunisian patients with atopy and 81 healthy control subjects. Results: Analysis of TAP1 polymorphism in T unisian patients with atopy and in unaffected control subjects demonst rates a high relative risk (RR) of atopy in carriers of a codon (d) co rresponding to a glycine at position 637 of the TAP1-B and TAP1-D alle les. The relative risk of allergic asthma is markedly higher in homozy gotes (d/d) (RR = 22; p less than or equal to 0.0001). The TAP1-D alle le, not observed in European populations, has a frequency of 5% in the Tunisian control subject group. A major increase of the frequency (f) of the D allele is observed in patients with allergic asthma (f = 35% ) and in those with allergic rhinitis (f = 22%), indicating a high rel ative risk of allergic asthma (RR = 10.2; p less than or equal to 0.00 01) and of allergic rhinitis (RR = 5.4; p less than or equal to 0.005) in individuals carrying this allele. DD homozygotes were found only a mong patients with allergic asthma (23% of patients with asthma). Furt her evidence of the strong association between TAP1 polymorphism and a topy was provided by the finding that atopy is transmitted by inherita nce of the glycine-637 marker. Conclusions: Tunisian persons carrying the glycine-637 of the TAP1 protein may have an increased risk of atop y. Specific association was found between the homozygous TAP1 D/D geno type and allergic asthma.