Genetic markers linked to rheumatoid arthritis are also strongly associated with articular manifestations in ulcerative colitis patients.

Ulcerative colitis is often accompanied by the development of extraintestinal, mainly articular, manifestations. Genetic differences could be underlying that clinical heterogeneity. We performed a case-control study to determine whether TNFab microsatellites or HLA-DR alleles were associated with the development of articular manifestations in patients with ulcerative colitis. With that aim, a total of 84 ulcerative colitis patients with articular manifestations and 172 without them were genotyped for TNFab microsatellites and HLA-DR. A healthy control sample (n = 595) was also included for comparative purposes. Haplotypes were inferred with the Arlequin software. The influence of HLA-DRB1*0103 and HLA-B27, factors previously known to be associated with extraintestinal manifestations, was specifically addressed. We observed that TNFa6b5 minihaplotype increases the susceptibility to developing articular manifestations in ulcerative colitis patients (p = 0.003, OR = 2.39). The locus HLA-DR does not appear to be involved in these extraintestinal manifestations by itself; however, the frequency of subjects carrying TNFa6b5 in combination with DR1, DR7, or DR11 is very significantly increased in patients with articular manifestations (p = 3.9 x 10(-8)). The associations found were independent of DRB1*0103 and HLA-B27. Thus, it seems that the development of articular manifestations in ulcerative colitis patients appears to be influenced by some genetic factor(s) present in some major histocompatibility complex haplotypes.