Predicting Susceptibility to Celiac Disease by Genetic Risk Profiling

Review Article

Predicting Susceptibility to Celiac Disease by Genetic Risk Profiling

Jihane Romanos and Cisca Wijmenga

Affiliation: ¹Department of Genetics, University Medical Center Groningen, University of Groningen


ABSTRACT

Celiac disease (CD) is a common, immune‐mediated, intestinal disorder with a prevalence of approximately 1% in Caucasians. An important and necessary genetic risk factor is HLA‐DQ2. Dietary gluten is the triggering environmental factor, and a lifelong gluten‐free diet is currently the only treatment for CD. CD is officially diagnosed by serology followed by a small intestinal biopsy. However, the majority of CD patients go undiagnosed as the symptoms associated with CD can be rather subtle, and many patients remain at a silent or latent stage. As CD is associated with increased morbidity and mortality, it puts a severe socio‐economic burden on patients, their families, and society. Improved diagnosis of CD and early intervention would alleviate, or reverse, these negative effects. The recent identification of part of the genetic risk for CD may help in diagnosing individuals at high risk for CD before the disease manifests. In this review, we show how genetic knowledge can be applied as a diagnostic or screening tool to prevent comorbidity and long‐term complications. We envision a two‐step approach. First, based on human leukocyte antigen (HLA) typing, we can exclude individuals with no HLA‐DQ2/DQ8 as they have no risk of developing CD. Second, we can combine the presence of HLA‐DQ2/DQ8 with the non‐HLA genetic risk factors and classify the remaining individuals into low (<0.1%), intermediate (0.1–7%), and high (>7%) risk groups. Individuals in both the intermediate‐ and high‐risk groups should undergo serology and biopsy testing. Our prediction model for CD will lead to improved diagnostic and prevention strategies.

Keywords: celiac disease, genetic profile, predictive test, human leukocyte antigen (HLA), gluten intolerance, gluten sensitive enteropathy, celiac sprue

Correspondence: Cisca Wijmenga, Department of Genetics, University Medical Centre Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands. Tel: (31)‐(0)50‐361‐7100; Fax: (31)‐(0)50‐361‐7230; e‐mail: c.wijmenga@medgen.umcg.nl