What is coeliac disease?
Coeliac disease is an autoimmune disorder (a condition when a person’s own immune system starts attacking various tissues in the body) of the small intestine. It occurs in genetically predisposed people of all ages. Symptoms include diarrhoea, fatigue, upset stomach and bloating, but the disease may also be asymptomatic. Coeliac disease is caused by a reaction to gliadin, a gluten protein found in wheat. Similar proteins are also found in barley and rye. The only effective treatment is a gluten-free diet.
Role of genes in the development of coeliac disease
HLA or human leukocyte antigens are a group of genes that reside on the short arm of chromosome 6. They produce proteins that are actively involved in various immune reactions. These proteins reside on cells of the immune system and thus can directly influence the body’s immune reactions to foreign and unknown substances.
The development of this disease depends significantly on the interaction between the environment and the genes that cause coeliac disease. The results of many studies show that this disease may occur in individuals who carry two HLA gene variants – HLA-DQ2 and/or HLA-DQ8. The most important environmental factor is, of course, the consumption of food products containing gluten. Patients with coeliac disease:
in 97% of cases have a positive test result for one or both of the above-mentioned genes;
in 90% of cases have a positive test result for DQ2 gene variants;
less than 10% of cases have a positive test results for DQ8 gene variants.
Even if a person has been diagnosed with these so-called “coeliac disease genes” (which should in fact be called “gene variants”), this does not mean that they will definitely develop coeliac disease. It simply indicates that the person has an increased risk for coeliac disease.
If a person does not have these gene variants, the probability of developing coeliac disease at any point of life is extremely low or non-existent.
Who should have a DNA test for coeliac disease risk performed?
People who already are on a gluten-free diet. In comparison with the antibody test and biopsies, the genetic test is accurate even in people who are on a gluten-free diet.
People who have not had a small intestine biopsy performed, but who have been on a long-term gluten-free diet. A positive result in the genetic test increases certainty that the symptoms that served as a basis for starting a gluten-free diet were actually caused by coeliac disease, but does not confirm the diagnosis. The only way to confirm a diagnosis of coeliac disease is to stop a gluten-free diet and undergo a biopsy of the small intestine. A negative test result does not exclude but indicates the low probability of such a diagnosis. Consideration of differential diagnoses is advisable.
Relatives of patients with coeliac disease. If any of your relatives have had coeliac disease, your odds of developing this condition at some point in your life are 1:22. If a second-degree relative of yours has had coeliac disease, your odds are 1:39*. People in whom the gene variants that cause coeliac disease are detected should have their antibody levels checked regularly, even if they are not symptomatic. Regular monitoring will allow early detection of coeliac disease.
Patients for whom a biopsy of the small intestine is inconclusive. If biopsy results are inconclusive, but the patient has a negative result for DQ2 and/or DQ8 variants, coeliac disease can be excluded with the highest probability rate.
Description of the DNA test for coeliac disease risk and interpretation of results
There are several types of coeliac tests worldwide. They have different methodologies and degrees of accuracy in detecting gene variants.
Our laboratory is the only one in Latvia to offer HLA gene variant detection by means of the sequencing method. This test provides the most accurate data on the presence of the above-mentioned gene variants that may increase the risk of coeliac disease.
Interpretation of the HLA-DQ2 and DQ8 tests
HLA-DQ2 and DQ8 are proteins with two chains – an alpha and beta chain. These chains are encoded by two genes: the DQA1 gene that creates an alpha chain of the DQ molecule, and the DQB1 gene that creates a beta chain of the DQ molecule. These genes combine in many variants and such combinations may result in DQ2 and DQ8 gene variants.
The DQ2 molecule is formed by the following combinations of DQA1 and DQB1 gene variants:
DQ2.2 – DQA1*0201 + DQB1*0202 (low % of association with coeliac disease)
DQ2.3 – DQA1*0303 + DQB1*0202 (association with coeliac disease has not been described)
DQ2.5 – DQA1*0501 + DQB1*0201 (risk factor for coeliac disease)
The DQ8 molecule is formed by:
DQ8.1 – DQA1*0301 + DQB1*0302 (associated with coeliac disease)
DQ8.1v – DQA1*0302 + DQB1*0302 (associated with coeliac disease)
DQ8.4 – DQA1*0401 + DQB1*0302 (a rare variant, association with coeliac disease has not been described)
DQ8.5 – DQA1*0503 + DQB1*0302 (a rare variant, association with coeliac disease has not been described)
If a patient demonstrates combinations of gene variants that indicate DQ2 or DQ8 gene variants, he or she has an increased risk of developing coeliac disease.
*Data from the Chicago Celiac Disease Centre