Genetic and exogenous causes of celiac disease

  1. Dr.Schär Institute
  2. Dr. Schär Institute
  3. Genetic and exogenous causes of celiac disease
DNA, Genetik, Exogene Ursachen, Pathogenese

Celiac disease has a complex pathology resulting from interaction between a number of genetic and exogenous factors.

Genetic factors

A high incidence of celiac disease within affected families (approximately 10% among first-degree relatives and 80% among twins) suggests a genetic involvement in the pathogenesis of celiac disease [5]. An important genetic factor is the human leukocyte antigen (HLA) system, a gene complex whose task is to recognize foreign molecules. 90% of celiac patients carry genes encoding HLA DQ2, while most of the remainder carry the HLA DQ8 haplotype [1]. Although these are necessary for the disease to develop, they are not solely responsible for it. It is known that these genes are also present in up to 40% of individuals in Western populations, however, the frequency is population dependent [2].

Exogenous factors

The presence of gluten in the diet is clearly a pre-requisite for the development of celiac disease. Recent weaning guidelines have recommended that it may be prudent to avoid both early (<4 months of age) and late (>7 months of age) introduction of gluten and to introduce gluten while infants are still being breastfed [3,4]. However, these recommendations were based largely on observational data and more recently a number of new randomised control studies have been published in this area. Data from such studies appears to indicate that exclusive or any breastfeeding, including breastfeeding at the time of gluten introduction does not reduce the risk of developing coeliac disease during childhood. Moreover, for infants at higher risk of developing celiac disease, gluten introduction at 4 months of age, or at 6-12 months of age results in similar rates of celiac disease diagnosis in early childhood [5].

Connection to other diseases

There are some autoimmune diseases, e.g. Type 1 diabetes, that have a high occurrence among celiac disease patients when compared to the non celiac general population. For these conditions, screening is advisable in order to detect possible celiac disease, even if there are no clear symptoms.




  1. Fasano, A., Catassi, C. (2012). Clinical practice. Celiac disease. N Engl J Med.;     20; 367(25):2419-26. doi: 10.1056/NEJMcp1113994.
  2. Celiac disease: past, present, and future challenges: dedicated to the memory of our friend and colleague, Prof David Branski (1944-2013). Heyman MB. J Pediatr Gastroenterol Nutr. 2014 Jul;59 Suppl 1:S1. doi:10.1097/01.mpg.0000450390.38403.22
  3. Dabelea D, Mayer-Davis EJ, Saydah S et al. Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA 2014; 311:1778-1786
  4. Scaramuzza AE, Mantegazza C, Bosetti A, Zuccotti GV. Type 1 diabetes and celiac disease: The effects of gluten free diet on metabolic control. World J Diabetes 2013; 4: 130-134
  5. Husby S, Koletzko S, Korponay-Szabó IR et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54: 136-160
  6. Fröhlich-Reiterer EE, Kaspers S, Hofer S, et al. Anthropometry, metabolic control, and follow-up in children and adolescents with type 1 diabetes mellitus and biopsy-proven celiac disease. J Pediatr 2011; 158: 589-593.
  7. Akirov A, Hirsch G, Boyko V, et al. Celiac in type 1 diabetes children and youth–prevalence, metabolic control and growth parameters. Tel Aviv: Israel Society of Clinical Pediatrics, 2010
  8. Leeds JS, Hopper AD, Hadjivassiliou M, Tesfaye S, Sanders DS. High prevalence of microvascular complications in adults with type 1 diabetes and newly diagnosed celiac disease. Diabetes Care 2011; 34: 2158-2163
  9. Hansen D, Brock-Jacobsen B, Lund E, et al. Clinical benefit of a gluten-free diet in type 1 diabetic children with screening-detected celiac disease: a population-based screening study with 2 years’ follow-up. Diabetes Care 2006; 29: 2452-2456
  10. Mohn A, Cerruto M, Iafusco D, et al. Celiac disease in children and adolescents with type I diabetes: importance of hypoglycemia. J Pediatr Gastroenterol Nutr 2001; 32: 37-4
  11. Mollazadegan K, Kugelberg M, Montgomery SM, et al. population-based study of the risk of diabetic retinopathy in patients with type 1 diabetes and celiac disease. Diabetes Care 2013; 36: 316-321
  12. Pitocco D, Giubilato S, Martini F, et al. Combined atherogenic effects of celiac disease and type 1 diabetes mellitus. Atherosclerosis 2011; 217: 531-535
  13. Mollazadegan K, Sanders DS, Ludvigsson J, Ludvigsson JF. Long-term coeliac disease influences risk of death in patients with type 1 diabetes. J Intern Med 2013; 274: 273-280