HLA-DQ and risk gradient for celiac disease

Celiac disease (CD) is a rare example of multifactorial disorder in which a genetic test is of great clinical relevance, as the disease rarely develops in the absence of specific HILA alleles. We typed DR-DQ genes in 437 Italian children with celiac disease, 834 first-degree relatives, and 551 controls. Of patients, 91 % carried DQ2 and/or DQ8 heterodimers, 6% only had)32 chain, 2% was alpha 5 positive, and four were DQ2/DQ8/beta 2/alpha 5 negative. Only the presence of alpha 5 resulted negatively associated to disease (p = 2 X 10(-4)), whereas we confirmed the effect of the beta half of DQ2 dimer on CD predisposition (p = 4 x 10(-12)). Considering 1:100 disease prevalence, we obtained a risk gradient ranging from 1:7 for DQ2 and DQ8 individuals down to 1:2518 for subjects lacking all predisposing factors. The DQB1*02 and DQB1*0302 concurrence (p = 9 X 10-4), besides the DQB1*02/*02 homozygosity, had an additional role in disease genetic determination. The CD prevalence rose to 17.6% in sisters, 40.8% in brothers, and 3.4% in parents. In the three groups, the subjects carrying high-risk HLA molecules were 57%, 71%, and 58%; among them, 29%, 15%, and 6% respectively had CD. Those siblings and parents with no susceptible factors were not affected. These findings indicate the impact of the HLA test for CD in clinical practice. (0 2009 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics