13th IHWS Disease Component Joint Report: D6. The 13th International Histocompatibility Working Group for Celiac Disease Joint Report

Genetic risk factors for celiac disease are located within the HLA complex, where the genes encoding the DQ molecules are known to be primarily involved. The aim of this collaborative effort was to look for evidence of additional predisposing loci in the HLA complex. A total of 517 patients, 925 unrelated controls and 365 families including at least one celiac patient were investigated by using 12 microsatellite markers throughout the extended HLA complex. Genotype information for DR and DQ loci was also available. In order to exclude associations secondary to linkage disequilibrium with DQ alleles, the association tests were performed after controlling for these loci. We found evidence for additional disease influencing loci in the HLA complex besides DQA1 and DQB1. In particular on the DQ2-DR3 haplotype, markers carried on the DQ2-DR3-B8 haplotype (i.e. TFNd*131 and MIB*361) suggested increased risk, while those characteristic of the DQ2-DR3-B18 haplotype (i.e. TNFd*137 and MIB*336) were reduced among patients compared to controls. While on the DQ2-DR7 and DQ7-DR11 haplotypes, the microsatellite D6S265 (near HLA-A) showed association. Taken together, our data showed that there exist yet unidentified loci in the HLA complex predisposing to celiac disease.