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Annual for Hospital Pharmacy

Genetics Of Gluten Intolerance

Olga Antonova


Celiac disease, or extreme gluten intolerance, is an autoimmune disease that primarily causes damage to the small intestine. It is caused by dietary intake of gluten in genetically predisposed individuals. The presentation of celiac disease consists of digestive tract symptoms, mainly diarrhea and subsequent weight loss. Other related symptoms and findings are iron deficiency anemia, decreased bone density, and some nonspecific neurological symptoms.

In the recent past, the diagnosis of celiac disease was made based on specific serological tests, small intestinal mucosa biopsy results, and fading away of symptoms after gluten-free diet is applied.

After the identification of the disease-specific genes HLA-DQ2 and DQ8, genetic testing was considered the gold standard for the diagnosis of celiac disease, because the presence of a specific genotype is a prerequisite for the development of this disease. Risk variants of HLA-DQ2 and DQ8 are found in about 30% of the general European population. Determining the genetic status allows adequate subsequent clinical decisions. The lack of genetic variants predisposing to celiac disease leads to the exclusion of the diagnosis, while the detection of high-risk variant(s) in an individual prompts additional diagnostic steps through a number of serological and invasive tests. The introduction of genetic analysis has led to a significant reduction in the number of invasive intestinal tests (biopsies).

The purpose of this article is to present the current practical approach in the diagnosis of celiac disease, which includes mandatory genetic analysis, and to explain the nature of this autoimmune disease from a genetic point of view.


celiac disease, genetic analysis, nutrigenetics

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Troncone, R. and B. Jabri, Coeliac disease and gluten sensitivity. J Intern Med, 2011. 269(6): p. 582-90.

Mustalahti, K., et al., The prevalence of celiac disease in Europe: results of a centralized, international mass screening project. Ann Med, 2010. 42(8): p. 587-95.

Wessels, M.M.S., et al., Towards an individual screening strategy for first-degree relatives of celiac patients. Eur J Pediatr, 2018. 177(11): p. 1585-1592.

Singh, P., et al., Risk of Celiac Disease in the First- and Second-Degree Relatives of Patients With Celiac Disease: A Systematic Review and Meta-Analysis. Am J Gastroenterol, 2015. 110(11): p. 1539-48.

Nistico, L., et al., Concordance, disease progression, and heritability of coeliac disease in Italian twins. Gut, 2006. 55(6): p. 803-8.

Liu, E., et al., Risk of pediatric celiac disease according to HLA haplotype and country. N Engl J Med, 2014. 371(1): p. 42-9.

Parzanese, I., et al., Celiac disease: From pathophysiology to treatment. World J Gastrointest Pathophysiol, 2017. 8(2): p. 27-38.

Rampertab, S.D., et al., Trends in the presentation of celiac disease. Am J Med, 2006. 119(4): p. 355 e9-14.

Ludvigsson, J.F. and P.H. Green, Clinical management of coeliac disease. J Intern Med, 2011. 269(6): p. 560-71.

Lebwohl, B., D.S. Sanders, and P.H.R. Green, Coeliac disease. Lancet, 2018. 391(10115): p. 70-81.

Husby, S., et al., European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr, 2012. 54(1): p. 136-60.

Rubio-Tapia, A., et al., ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol, 2013. 108(5): p. 656-76; quiz 677.

Mungall, A.J., et al., The DNA sequence and analysis of human chromosome 6. Nature, 2003. 425(6960): p. 805-11.

Wolters, V.M. and C. Wijmenga, Genetic background of celiac disease and its clinical implications. Am J Gastroenterol, 2008. 103(1): p. 190-5.

Sapone, A., et al., Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med, 2011. 9: p. 23.

Habig, D.F., et al., Donor-specific antibody to trans-encoded donor HLA-DQ heterodimer. Hum Immunol, 2015. 76(8): p. 587-90.

Molberg, O., et al., Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat Med, 1998. 4(6): p. 713-7.

van de Wal, Y., et al., Selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity. J Immunol, 1998. 161(4): p. 1585-8.

Jabri, B. and L.M. Sollid, Mechanisms of disease: immunopathogenesis of celiac disease. Nat Clin Pract Gastroenterol Hepatol, 2006. 3(9): p. 516-25.

Megiorni, F., et al., HLA-DQ and risk gradient for celiac disease. Hum Immunol, 2009. 70(1): p. 55-9.

Almeida, L.M., et al., Presence of DQ2.2 Associated with DQ2.5 Increases the Risk for Celiac Disease. Autoimmune Dis, 2016. 2016: p. 5409653.

Mubarak, A., et al., Human leukocyte antigen DQ2.2 and celiac disease. J Pediatr Gastroenterol Nutr, 2013. 56(4): p. 428-30.

Fallang, L.E., et al., Differences in the risk of celiac disease associated with HLA-DQ2.5 or HLA-DQ2.2 are related to sustained gluten antigen presentation. Nat Immunol, 2009. 10(10): p. 1096-101.

Bodd, M., et al., T-cell response to gluten in patients with HLA-DQ2.2 reveals requirement of peptide-MHC stability in celiac disease. Gastroenterology, 2012. 142(3): p. 552-61.

Karell, K., et al., HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer: results from the European Genetics Cluster on Celiac Disease. Hum Immunol, 2003. 64(4): p. 469-77.

Vader, W., et al., The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses. Proc Natl Acad Sci U S A, 2003. 100(21): p. 12390-5.

Karinen, H., et al., Gene dose effect of the DQB1*0201 allele contributes to severity of coeliac disease. Scand J Gastroenterol, 2006. 41(2): p. 191-9.

Biagi, F., et al., Influence of HLA-DQ2 and DQ8 on severity in celiac Disease. J Clin Gastroenterol, 2012. 46(1): p. 46-50.

Al-Toma, A., et al., Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma. Clin Gastroenterol Hepatol, 2006. 4(3): p. 315-9.

Brown, N.K., et al., A Clinician's Guide to Celiac Disease HLA Genetics. Am J Gastroenterol, 2019. 114(10): p. 1587-1592.

Karinen, H., et al., HLA genotyping is useful in the evaluation of the risk for coeliac disease in the 1st-degree relatives of patients with coeliac disease. Scand J Gastroenterol, 2006. 41(11): p. 1299-304.



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