Genetics of Celiac

Genetics of Celiac

Created On
Nov 24 2021
Last Updated
May 17 2023


Celiac disease is an intolerance to gluten, which results in damage to the lining of small intestinal, on exposure to foods containing gluten.

Symptoms include abdomen pain, bloating, diarrhea, fatigue, and mouth sores. If continued, one may suffer from weight loss, lower bone mineral density, iron and vitamin D deficiency, and short stature.

Gluten contact with intestinal lining causes inflammation and damages the nutrient absorbing surface. This significantly reduces the surface, and amount of fluid secreted, making it difficult to digest food, eventually resulting in mal-absorption and destruction of intestinal lining.

The problem starts with high amount of proline—large chunks of certain proteins in foods—mainly wheat, barley, and rye, that are harder to break down and digest in the intestine.

An enzyme called tissue trans-glut-aminase (tTG) converts these undigested protein fragments into a form that binds to certain antibodies. Antibodies are molecules that immune system produces to fight alien substances in the body, e.g., bacteria and viruses.

Role of Genes

For celiac, the DQ2, DQ8 genes produce antibodies that bind to gluten molecules. In order to cause gluten intolerance, these genes are essential.

The gluten from food binds to the cells through a dimer—a two-armed molecule with alpha and beta chains, each of which is formed by an independent gene. Both arms may form by genes inherited from one parent, or each parent may contribute one-half.

Because these genes transfer from parents to children, celiac runs within families. In fact, half of first-relatives, of people with DQ2 or DQ8 genes, might inherit them and be at risk of gluten sensitivity.

Although nearly 1% of population in US and Europe has celiac, gluten sensitivity in affected families is much higher, at 5 to 15%.

Studies of identical twins show that in 70-75% cases, both twins were affected whenever one had celiac. That’s more than any other auto-immune disease, including Type 1 diabetes (36%), Crohn's disease (33%), and multiple sclerosis (25%).

Almost 90-95% celiac positive cases involve DQ2. But a small portion, 5-10% cases, also carry DQ8. This combination of DQ2 and DQ8 covers almost all cases; although 39 genes have so far been implicated in gluten intolerance.

Although essential, presence of these genes is not a guarantee of testing positive for celiac—reasons for that are not yet understood. However, MassGeneral says "3 out of every 100 people who carry a gene for celiac disease will go on to develop the disease."

It is extremely rare to find celiac disease (0.04%) in people who do not have the relevant genes. Therefore, a negative result is extremely valuable.

Certain genes are dominant. For example, a higher chance of DQ2 genes in the overall DQ system increases the chances of celiac. Studies show that only about 2% positive cases have DQB1 genes—the one forming beta chain of dimer—but they may be almost 25% of known celiac cases.

Close to 40% of the western population has DQ2 or DQ8 genes; though positive cases remain low at approximately 1%. It is rare to find cases with one of the other 39 genes and they show much lower correlation.

Role of Testing

In 2012, the New England Journal of Medicine suggested, "testing for HLA-DQ2 and HLA-DQ8 may be useful in at-risk persons (e.g., family members of a patient with celiac disease)". Such testing has a "high-negative predictive value, which means that the disease is very unlikely to develop in persons who are negative for both HLA-DQ2 and HLA-DQ8". In fact, "Up to 97% of cases", the HLA phenotypes are prerequisite for celiac.

A 2019 Mayo Clinic study had similar conclusion, calling for screening of family members. The Celiac Foundation recommends testing "family members, especially children, to prevent future unnecessary testing" and "screening gene-positive first-degree relatives every 3-5 years".

There is no cure of celiac and we cannot control our genes. But with a few simple steps we can test to learn if we have inherited them.


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