Celiac disease is caused by an interaction between genes and environment. Very strong evidence shows that in order to develop celiac disease, a person must have one or both of two genes known as HLA-DQ2 and HLA-DQ8. The major environmental factor, of course, is gluten ingestion. Gluten proteins interact with the celiac disease genes to trigger an abnormal immune response that damages the lining of the small intestine.
More than 97% of patients with celiac disease have at least one of the two genes. Most patients (more than 90%) carry the DQ2 gene. Fewer than 10% carry the DQ8 gene. In the near future, researchers will likely discover additional genes that predispose an individual to celiac disease.
How Can You Get Tested for the Genes that Predispose You to Celiac Disease?
Several types of DNA tests for genes that predispose to celiac disease are available, using either a blood sample, or cells obtained by swabbing the inside of your cheek. Your doctor can arrange a test for you, or you can order a test kit by mail from Kimball Genetics, with one-day turnaround and genetic counseling included.
What a DNA Test for Genes Can and Can’t Tell You
A DNA test cannot confirm a diagnosis of celiac disease. It can only show whether or not a person has the genes that predispose to this disorder. Just because a person has DQ8 or DQ2, it does not mean that celiac disease is inevitable. It just means this person might develop a sensitivity to gluten.
Without the DQ2 or DQ8 genes, however, a person is extremely unlikely to develop celiac disease.
Who Might Benefit from Genetic Tests for Celiac Disease?
- People who are already on a gluten-free diet. Unlike antibody tests and small intestine biopsies, DNA testing is accurate even when a person is already on a gluten-free diet. For this reason, a genetic test can be useful in patients who have not had a small-intestine biopsy to diagnose celiac disease but who have been gluten-free for a long time. A positive test would increase the likelihood that their symptoms were caused by celiac disease, but would not prove it. (The only way to prove the diagnosis would be to have them resume eating gluten and then undergo a biopsy.) A negative genetic test, however, would mean they don’t have celiac disease.
- Relatives of people with celiac disease. According to the University of Chicago Celiac Disease Center, if you are a first-degree relative (parent, child, or sibling) of a person with celiac disease, you have a 1 in 22 chance of developing the disease in your lifetime. If you are a second-degree relative, (aunt, uncle, niece, nephew, grandparent, grandchild, or half-sibling), your risk is 1 in 39. First- and second-degree relatives who have genetic testing and discover they have the celiac genes can have their antibody levels checked regularly, even if they have no obvious signs of the disease. Regular monitoring will allow the disease to be diagnosed quickly if it does develop. Early diagnosis in turn will reduce the risk of associated complications. On the other hand, if you do not carry the genes, then you are at extremely low risk for developing celiac disease, and your children are at extremely low risk as well (unless they have inherited the DQ8 or DQ2 gene from their other parent).
- People with unclear small bowel biopsy results. If the results of the biopsy are not conclusive and the patient does not have either the DQ8 or DQ2 gene, celiac disease is very unlikely.
In all cases, DNA tests should be accompanied by genetic counseling and should be done with the knowledge of your doctor. (In fact, if your doctor does not approve the testing in advance, you may have trouble getting reimbursed by your insurance company.) If counseling is not already included with your test, ask your doctor to recommend a counselor, or contact the National Society of Genetic Counselors or the American Board of Genetic Counseling for information.
Sources:
Torres MI, López Casado MA, Ríos A. New aspects in celiac disease. World Journal of Gastroenterology 2007; 13: 1156-61.
Louka AS, Sollid LM.
HLA in coeliac disease: unravelling the complex genetics of a complex disorder. Tissue Antigens 2003; 61:105-17.
NIH Consensus Development Conference on Celiac Disease: Consensus Conference Statement.
