Ten Facts About Celiac Disease Genetic Testing
Dr. Scot Lewey is a digestive disease specialist doctor (board certified gastroenterologist) whose medical practice focuses on digestive and food related illness & research. He has published numerous articles, many of which are featured in popular Celiac newsletters. Not only is he a medical expert on food allergy & intolerance but he is also personally sensitive to gluten & dairy, & his wife has Celiac disease. They live gluten free in Colorado.View all articles by Dr. Scot Lewey
The absence of any portion of the high-risk genetic patterns DQ2 and DQ8 nearly excludes the possibility of celiac disease with an approximate accuracy of 99.9%. However, there is a big caveat about relying on "negative celiac genetic testing". To definitively declare you have negative celiac genetic tests requires that the laboratory test for and report the presence or absence of the entire HLA DQ genetic pattern, including both alpha and beta subunits. The DQ genetic patterns DQ2 and DQ8 have two subunits but some laboratories only test for the beta subunit. This DQ typing is complicated and difficult to understand even by physicians and scientists. I have written an updated detailed review that appears in the Spring 2008 issue of Scott-Free newsletter published by celiac.com.
Data collected by Dr. Ken Fine of Enterolab has supported the well-known fact that the absence of DQ2 and DQ8 does not exclude the risk of being gluten intolerance or sensitive though it now generally believed that one or both of those genetic white blood cell patterns are required to develop the autoimmune disorder known as Celiac disease or Celiac Sprue. However, there is a new study that reports that being negative for DQ2 and DQ8 does not completely exclude the possibility of celiac disease, especially in men. Previous studies have well documented blood test negative Celiac Sprue, also more common in elderly men with long-standing severe disease. Since DQ2 or DQ8 is almost universally present with the specific blood tests tissue transglutaminase and anti-endomysial antibodies are present it is not surprising that individuals without DQ2 or DQ8 that are negative for these two blood tests are being reported that meet criteria for Celiac disease.
These new studies are also providing further information that the genetics of Celiac is gender specific. If you are a man, your risk of celiac disease may be higher than a woman if you don't have the classic genetic patterns. Again, in this situation your blood tests may be negative. If you are a woman, the risk for Celiac disease is generally higher than a man, especially if you have received the at risk gene from your father instead of your mother.
Celiac is arguably the most common autoimmune disease. It is very common. It is easily treated. It affects 1/100 people worldwide. However, most people with celiac disease (~90%) are unaware, undiagnosed or misdiagnosed. Most adults finally diagnosed with celiac disease have suffered at least 10-11 years and have seen more than 3 or more doctors. Genetic testing is not only available but can be extremely helpful in determining your risk of developing Celiac disease, how severe it may be and the risk of your family members. Don't be one of those whose diagnosis is missed or needlessly delayed for over a decade. Get tested! Learn about the genetic tests for Celiac disease and if necessary educate your doctor about this testing.
Here are ten facts you should know and remember about Celiac genetic testing.
- Genetic testing can help determine your risk as well as your children's risk.
- Celiac genetic tests can be done on blood or a mouth swab sample but your doctor may be unaware of the tests, not know how to order them, or know how to interpret the results.
- Genetic testing is not affected by diet. You can be eating gluten or on a gluten free diet. Blood tests for celiac disease antibodies, however, need to be done while eating gluten. They can become negative within a few weeks of restricting gluten so if you are going to get the diagnostic antibody blood tests don't begin a gluten free or restricted diet before being tested.
- Some insurance companies do not for the Celiac genetic test and almost all who do require pre-authorization first. The following diagnostic codes are helpful when requesting insurance coverage: 579.0 (Celiac disease); V18.59 (family history of GI disease); and/or V84.89 (genetic susceptibility to disease).
- Some laboratories do not perform the all of the necessary components of the test to completely exclude the possible genetic risk of Celiac disease and most don't test for or report the other gluten sensitive DQ patterns. Before you accept that have a negative test you need to know if your test included both the alpha and beta subunits of HLA DQ or did they just perform the beta typing.
- In some rare individuals, especially some men, a negative genetic test may not exclude the possibility of celiac disease anymore than a negative blood test. Men more commonly have negative genetic tests and blood tests, especially older men with long-standing severe disease.
- Both the DQ type, and number of copies you have, matter when determining not only your risk but also the possible severity of celiac disease. Two copies of DQ2 carries more risk than one copy of DQ8 or only partial DQ2. Even a single copy of DQ2 alpha subunit ("half DQ2 positive") carries risk for celiac disease but most of the commonly used laboratories for Celiac genetics do not test for or report the presence of this component of the celiac genes.
- The absence of at risk genes DQ2 and/or DQ8 does not exclude the possibility of being gluten intolerant or sensitive. You may respond to a gluten free diet even if you don't have DQ2 or DQ8 or true autoimmune Celiac disease.
- You can get genetic testing without a doctor's order and the tests can be done without having blood drawn or insurance authorization if you are willing to pay between $150-400 (www.kimballgenetics.com and www.enterolab.com).
- Laboratories in the U.S. that are known to offer complete alpha and beta subunit genetic testing include Kimball Genetics, Prometheus, and LabCorp. Bonfils, Quest and Enterolab only test for the beta subunit portions and therefore their test can miss part of a minor alpha subunit that carries a risk of Celiac disease. A negative DQ2 and DQ8 report from these labs may not necessarily be truly negative for the risk of Celiac disease.
- HLA-DQ and Susceptibility to Celiac Disease: Evidence for Gender Differences and Parent-of-Origin Effects. Megiorni F et al. Am Journal Gastroenterol. 2008;103:997-1003.
- Celiac Genetics. Dr. Scot Lewey. Scott-Free, Spring 2008.
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