Lack of correlation between genotype and phenotype in celiac disease

Background: Celiac disease has a wide range of clinical features. The goal of this study was to evaluate whether specific HLA genotypes are associated with particular clinical appearances. Methods: One hundred forty- five patients with confirmed celiac disease were oligotyped for DR and DQ HLA genes. Clinical notes, physical examination, and a questionnaire provided their personal data. Patients were grouped into nine genotypic categories, according to the presence of the specific DQ heterodimer DQA1*0501- DQB1*0201 (hence termed α(o)β(o)) in single or double dose, and the presence of the DRB4 antigen. Results: Age at first symptoms and age at beginning of gluten-free diet were not significantly different in the nine groups. The initial symptoms of the disease had a similar distribution in all groups. In twenty-seven patients, disease was diagnosed by family screening: they shared a similar HLA genotype with those who had relevant symptoms. The actual growth status - evaluated by standardized height, percentage of median weight for age, and percentage of median weight for height - was not different in the nine groups. Presence of unusual health complaints was not associated with a specific genotype. Conclusions: There is no evidence that clinical features of celiac disease are associated with different HLA genotypes. Genes outside the HLA may play a relevant role.