Objective: Although HLA-B27 is strongly associated with susceptibility to Reiter's syndrome (RS), recent data suggest that an additional modifying or susceptibility gene(s) acts in concert with HLA-B27 to contribute to disease pathogenesis. The recently described TAP genes (transporters associated with antigen processing) are potential candidates because they are polymorphic and their function is to transport antigenic peptides to be loaded in HLA class I molecules.
Methods: TAP1 and TAP2 alleles were determined for 34 patients with RS (28 HLA-B27 positive, 6 HLA-B27 negative), and their frequencies were compared with those observed for 52 HLA-B27 positive and 80 random disease-free control subjects.
Results: The allele frequency of TAP1C was greater in patients with RS (8 of 62, 13%) than in random controls (5 of 160, 3%) (P = 0.009). The frequency of TAP2A was greater in RS patients (51 of 66, 77%) than in random controls (88 of 160, 55%) (P = 0.002); likewise, the frequency was greater in HLA-B27 positive RS patients (41 of 54, 76%) than in HLA-B27 positive disease-free controls (49 of 94, 52%) (P = 0.004). Furthermore, the TAP2A allele was present in all RS patients (100%), whereas TAP2A was present in 79% (63 of 80) of the random controls (P = 0.003).
Conclusion: The association observed between TAP alleles and RS is independent of the presence of HLA-B27, and despite the physical proximity of TAP and HLA class II genes, linkage disequilibrium does not account for the observed associations between TAP and RS. Thus, TAP genes are genetically separated but functionally linked to class I genes, and both contribute to susceptibility to RS.