TAP GENE TRANSPORTER POLYMORPHISM IN INFLAMMATORY BOWEL DISEASES

Background: Many studies suggest the implication of genetic factors in inflammatory bowel diseases. Despite some associations with HLA genes , the lack of definite data may be due to ethnic variations, clinical heterogeneity, or the involvement of additional susceptibility genes b eside or within the major histocompatibility complex (MHC), such as TA P genes. The aim of this study was to analyze in patients with ulcerat ive colitis (UC) or Crohn's disease (CD) the polymorphism of TAP genes that encode the proteins necessary for the transfer of antigenic pept ides through the endoplasmic reticulum membrane. Methods: One hundred and one UC and 148 CD patients were compared with 173 unrelated health y controls. Dimorphisms within the TAP1 and TAP2 alleles were analyzed by sequence-specific oligonucleotide typing. Results: No difference w as found between patient groups and controls. However, when CD patient s were classified on the basis of their responsiveness to steroid ther apy, a significant decrease of TAP2 AA (0101/*0101) genotype was foun d in CD patients who did not respond to steroid therapy (22.9% versus 33.7% in steroid responder group; Pc<0.05; odds ratio = 2.6; 95% confi dence limits (CL) = 1.2-5.9). These data appear independent of the dis tribution of HLA DRB101 or DRB1*03 alleles despite a significant link age disequilibrium between these alleles and TAP2A. Conclusions: This result suggests, despite the absence of arguments favoring a genetic s usceptibility to CD, that the TAP2 gene or other genes located on chro mosome 6 may be involved in the genetic heterogeneity of CD.