Celiac disease and TNF promoter polymorphisms

The possibility that genetic susceptibility to celiac disease (CD) might be influenced by tumor necrosis factor (TNF) genes polymorphism has repeatedl y been put forward. To date, this has only been investigated in case-contro l studies and results have been contradictory. In order to avoid any possib le ethnic mismatching between patients and controls, we have approached thi s problem studying 71 celiac families, establishing the parental haplotypes and comparing CD versus control haplotypes (the so-called AFBAC or affecte d family-based controls). We used DNA-based methods to screen for HLA-DRB1, -DQA1, and -DQB1 alleles, TNF alpha promoter polymorphims and TNFa and b m icrosatellites. The guanine-to-adenine polymorphism at position -308 of the TNF alpha gene promoter region was found associated with CD as the TNF-308 A allele appeared significantly increased in frequency in CD haplotypes, an d this was shown to be independent of the association between CD and the DR B1*0301,DQA1*0501,DQB1*0201 alleles. Our results indicate that at least ano ther gene, in addition to the known association of CD with HLA class II, ha s a susceptibility role in this disease. This should be either TNF alpha or another polymorphic gene in the telomeric end of the HLA class III region. Human Immunology 61, 513-517 (2000). (C) American Society for Histocompati bility and Immunogenetics, 2000. Published by Elsevier Science Inc.