| Celiac Disease |
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The primary DR/DQ associations with predisposition to the celiac disease have been extensively described in numerous studies but it is estimated to account for only approximately 35% of the genetic risk of developing the disease. The Celiac Disease (CD)Component of the IHWG aims at characterizing the influence of non-class II HLA genes on CD susceptibility. Preliminary data suggest the presence of an additional gene(s) telomeric to HLA-F locus on the DR3-DQ2 haplotype (Lie et al., Tissue Antigens 54: 162-68, 1999). It is very important to confirm and extend these results in other populations as well as for other disease predisposing HLA haplotypes. For example, we need to investigate whether such a protective gene on some DR3-DQ2 haplotypes may explain that in some populations DR3/DR7 heterozygous apparently are at higher risk to develop CD than DR3/DR3 homozygous. Further, we will look for contributions by genes in other parts in the HLA complex, in particular in the class III and class I regions. Genes in the HLA-complex will be investigated using a panel of microsatellite markers and single nucleotide polymorphisms (SNP). Technical details will be distributed in a short time. The case-controls approach will be performed in DRB1-DQA1-DQB1 fully matched samples typed as: DR3-DQ2/DR3-DQ2; DR3-DQ2/DR7-DQ2; DR3-DQ2/DR11-DQ3; DR7-DQ2/DR11-DQ3. DQ2 negative patients will be also characterised. Class II (DR/DQ) genotypes is a prerequisite for subject inclusion. The CD diagnosis must be based on intestinal biopsy/ies, according to the new European Society for Paediatric Gastroenterology and Nutrition (ESPGAN) criteria (Walker-Smith 1990). Information on clinical form of the disease, age at onset, presence of antibodies and associated autoimmune diseases will be requested. The IHWG offers a unique opportunity to collect families (simplex or multiplex) with at least one parent homozygous for CD-associated class II haplotypes. The analysis of the segregation of these haplotypes to the affected child appears the more appropriate method for studying the contribution to the development of the disease of genes in linkage disequilibrium with the CD predisposing class II alleles. DNA samples are required for at least the parents and the proband and will extend to other family members when possible. |
