Celiac disease predisposition

Celiac disease is an autoimmune disorder that can occur in genetically predisposed individuals, in whom the ingestion of gluten proteins present in wheat, barley and rye, or derivatives, causes damage to the villi of the small intestine.

It is estimated that 1% of the general population develops celiac disease. In Europe, the prevalence varies from 2% in Finland to 0.3% in Germany. All epidemiological studies indicate that celiac disease is more common in women than in men, with a 2:1 ratio, respectively.

Celiac disease can be diagnosed at any age. In children, symptoms such as diarrhea and malabsorption syndrome predominate. In adults, 75% of cases are diagnosed in women, with a peak incidence in the third decade and atypical symptoms, represented by iron deficiency anemia and prolonged nonspecific complaints.

Celiac disease is caused by an abnormal response to gluten. Gluten is partially digested in the intestine and the peptides produced, such as gliadin, can cause an inflammatory response in susceptible individuals. The immune response abnormally triggered by gluten causes pathological lesions in the intestinal epithelium, altering the structure of the intestinal villi and their main function, which is the absorption of nutrients.

Genetic predisposition to celiac disease is largely determined by the presence of HLA-DQ2.5 and HLA-DQ8 haplotypes, histocompatibility antigens that respond to the presence of gliadin (a peptide found in gluten), activating the immune response and releasing molecules with inflammatory activity.

Although more than 30 genes associated with the risk of celiac disease have been described, it is estimated that the presence of HLA heterodimers increases the risk of celiac disease by 25% to 30%.

Patients with celiac disease have at least one copy of the HLA-DQ2.5 and HLA-DQ8 haplotypes. The absence of HLA-DQ2.5 and HLA-DQ8 allows us to conclude that the person has no predisposition to develop celiac disease, therefore, the test has a negative predictive value. In other words, it allows us to determine which people will probably not develop the disease, which is of interest to differentiate it from pathologies with similar symptoms. The accuracy of its predictive value is very high, around 99%.

However, the HLA-DQ2.5 and HLA-DQ8 test does not serve to confirm the presence of celiac disease. For diagnosis, other tests such as serological tests, endoscopies and intestinal biopsies must be performed.

Number of observed variants

13.5 million variants

Number of variants analyzed in the study

2 variants

Bibliography

Asai Y., Eslami A., et al. Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy. J Allergy Clin Immunol. 2018 Mar;141(3):991-1001.

Czolk R., Klueber J., et al. IgE-Mediated Peanut Allergy: Current and Novel Predictive Biomarkers for Clinical Phenotypes Using Multi-Omics Approaches. Front Immunol. 2021 Jan 28;11:594350.

Hong X., Hao K., et al. Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children. Nat Commun. 2015 Feb 24;6:6304.

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