Celiac Disease Genetic Factors: How Important Are They?

Celiac Disease Genetic Factors: How Important Are They?
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Celiac Disease Genetic Factors

Celiac disease is a primarily gastrointestinal disorder in which the triggering factor is an inability to tolerate the gluten portion of wheat. (Gluten is a wheat protein which contains the polypeptide gliadin). Ingestion of gluten by celiacs leads to activation of the immune response,which results in damage to the walls of the small intestine by flattening villi.

The villi are a ‘carpet’ of finger-shaped extrusions of the intestinal lining which coats the small intestine: they enable and enhance absorption of nutrients. When they are flattened and damaged this affects the body’s take-up of nutrients and may lead to digestive problems and other symptoms. After the initial immune response the immune system then goes on to treat certain cellular molecules and enzymes belonging to the gut as invaders, which causes further damage.1

HLA And Genetic Factors In Gluten Intolerance

Signs and symptoms of celiac disease are not necessarily only gastrointestinal. Other symptoms and consequences can include nausea, loss of appetite, bloating and osteoporosis. The illness may also carry with it an increased risk of tumorous growths.3 An associated condition also seen in a percentage of celiac disease sufferers is dermatitis herpetiformis. This is a disfiguring and violently itchy skin condition.

Celiac disease is now accepted as having a strong genetic aspect to its causation. The HLA (Human Leukocyte Antigen) stretch of DNA is to be found on chromosome six and contains numerous genes significant in immune-related illness. It has been identified as containing genes having a definite association with development of celiac disease, without fully accounting for all genetic factors in the disease.1, p7 Other genes (both within the HLA and elsewhere on the genome) have been studied and identified as potentially implicated with respect to this sometimes serious disease, although with less definiteness than those in the HLA.1, p8

In trying to apportion relative responsibility of all celiac disease genetic factors, incidence of the disease in monozygotic twins has been compared with that in dizygotic twins who share the same HLA-located genetic risk factor (the latter being lower). The conclusion noted by F. Clerget Darpoux1 is that HLA genes cannot account for all genetic causation in CD. (He also concludes that twin studies demonstrate that all non-HLA causation is probably genetic. I would question whether this takes into account similar levels of gluten in sibling diets, as well as other shared environmental factors.)

Linkage Disequilibrium and Genetic Factors in Celiac Disease

A major problem in identifying other genetic causative factors in celiac disease, other than those found in HLA, is that of linkage disequilibrium. This describes the phenomenon in which groups of genes (which may not be related by any theme) are commonly expressed such that specific alleles are grouped close together on a chromosome. This makes it difficult to locate and identify the precise gene causing an effect in the body, e.g. by SNP (single nucleotide polymorphism) identification. An allele may be erroneously implicated in a condition merely due to an accident of location and co-expression.

Environmental Factors In Celiac Disease

If genetic factors are significantly causative in celiac disease, then what are the other risks? It has been suggested that environmental factors, e.g. diet or excessive levels of hygiene, may conceivably either aggravate or protect against development of celiac disease, working with or against the genetic factors. Studies of the disease in monozygotic twins have quoted the rate of co-incidence as approximately 70%1: but how do you account for the 30% of monozygotic twins studied in which only one twin is a sufferer, especially if their diets in the family home have been broadly similar?

It has been hypothesized that other physiological factors may interfere with or enhance the risk of development of celiac disease. For example, the inflammation caused by a viral infection may result in an immunological cascade that then is broadened to recognize and attack the body’s own receptors as antigens. Alternatively it is hypothesized that excessive hygiene and lowered rates of infections may result in less ‘competition’ between targets for the immune cascade, making it more likely that the body’s own cells and molecules will be attacked.

Coeliac Disease and Family Studies

Familial studies have been done to explore the view that genetic factors increase the risk of developing coeliac disease. Direct family members of sufferers have been quoted as having 4-12% likelihood of being sufferers themselves.3 International metastudies of national statistical reviews of familial and genetic risk factors in coeliac disease have also been done, looking at national differences in specific CD-related genotype occurrence in relation to the different haplotypes passing genetic material down generations.

Studies continue, looking to identify all the genetic risk factors for coeliac disease and to come up with new and more effective treatments for this disagreeable ailment. If you have related concerns or a family member with the condition, then your doctor is a good first port of call.


1. Cerf-Bensussan, N. “Coeliac disease: proceedings of the Xth International Symposium on Coeliac Disease.” Esher: John Libbey Eurotext, 2003

2. Van Heel, D.A. “A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21.” Nat Genet. 39.7 (July 2007): 827–829.

3. NDDIC. “Celiac Disease.” Digestive Diseases Home. September 2008. (23/02/2010) https://digestive.niddk.nih.gov/ddiseases/pubs/celiac/