Common HLA alleles, rather than rare mutants, confer susceptibility to coeliac disease

• Published in: Annals of human genetics 1999-05, Vol.63 (3), p.217-225
• Main Authors: BRETT, P. M., YIANNAKOU, J. Y., MORRIS, M-A., VAUGHAN, R., CURTIS, D., CICLITIRA, P. J.
• Format: Article
• Language: English
• Subjects: Alleles; Biological and medical sciences; Celiac Disease - genetics; Data Interpretation, Statistical; DNA - genetics; Family Health; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Predisposition to Disease; Genotype; HLA Antigens - genetics; HLA-DQ Antigens - genetics; Humans; Male; Medical sciences; Microsatellite Repeats; Mutation; Nuclear Family; Other diseases. Semiology; Pedigree; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
• ISSN: 0003-4800; 1469-1809
• DOI: 10.1046/j.1469-1809.1999.6330217.x

Coeliac Disease (CD) is a gluten sensitive enteropathy characterised by villous atrophy and crypt cell hyperplasia. It has a very strong HLA class II association to the DQ locus. The nature of the involvement of the DQ locus in the susceptibility to CD has been examined by tissue culture experiments, association and peptide binding studies. We examined the role of the DQ molecules in the pathogenesis from the perspective of a genetic family study. Using flanking microsatellite markers to the class II region of the MHC to establish the parental origin of the susceptibility DQ alleles, we have evidence suggesting that the HLA association is probably due to the necessity to have these DQ alleles in order to express CD and there is no support for the presence of a rare mutation within the DQ alleles nor any rare HLA-linked gene nearby in linkage disequilibrium with the DQ locus. This approach is applicable to other diseases demonstrating strong association with common alleles, and can be used to predict whether screening the region for rare mutations is likely to be worthwhile.