ASSOCIATION OF CELIAC-DISEASE WITH MICROSATELLITE POLYMORPHISMS CLOSETO THE TUMOR-NECROSIS-FACTOR GENES

Celiac disease is tightly linked to the MHC class II region on chromos ome 6. We have studied two highly polymorphic microsatellite loci, TNF a and b, near the TNF genes in the class III region of the MHC, for ev idence of their association to CD, as compared to a control population . Our findings show chat the microsatellite allele most significantly associated with the disease is TNFb3, which is found in 86.3% of CD pa tients versus 24.5% of controls, with allele frequencies of 0.5332 and 0.1290, respectively (P < 0.001). The TNFa2 allele had a frequency of 0.6122 in CD patients and 0.2627 in controls (p < 0.001), with phenot ype frequencies of 87.8% and 50.0%, respectively. TNFa6 and -all and T NFb5 have significantly reduced frequencies in CD patients. TNFb3 show s a maximal level of linkage disequilibrium with HLA-DQB10201 in celi ac patients. However, while the DQB10201/TNFa2 haplotype was strongly associated with CD, DQB10201 was not significantly in linkage disequ ilibrium with TNFa2, suggesting that TNFa2 is independently associated with CD, This association could have functional significance as TNFa2 has been correlated with high TNF production.