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    Ten Facts About Celiac Disease Genetic Testing


    Dr. Scot Lewey

    Celiac.com 04/24/2008 - Genetic tests for celiac disease and gluten sensitivity are readily available. Testing can be performed on either blood and mouth swab samples. If the testing is performed by certain laboratories not only will you have quite an accurate prediction of your risk of Celiac disease but also you may have information about the statistical probability that your children will inherit the risk, your likelihood of more severe Celiac disease, whether one or both of your parents had the risk gene, and for some laboratories you may determine your risk of gluten sensitivity without Celiac disease.

    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.

    1. Genetic testing can help determine your risk as well as your children's risk.
    2. 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.
    3. 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.
    4. 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).
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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).
    10. 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.
    References and Resources:
    • 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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    Guest Ann Stewart

    Posted

    Great info .........I never knew... always thought you had to have the intrusive biopsy test.

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    Guest Frances l Garcia,MD

    Posted

    Excellent: it explains why I am a severe celiac and yet am negative for the antibodies. I am a woman, northern European, Hispanic and Middle Eastern ethnicity and no previous known family history. My sons have tested negative for tTg and . My brother is negative for the tTg and antiendomyasial antibodies but has severe osteoporosis at 45 years of age, without any known risk factors. We need to do genetic testing!!

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    Guest Carina

    Posted

    Thank you. I need to get my kids tested, and I feel better knowing these things before I go in.

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    Guest Carri

    Posted

    Wow, very comprehensive yet easy to understand the 'genetics lingo.'

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    Guest sharon mackey

    Posted

    I had seven endoscopies done only 2 of them with same doctor---rest all different--celiac came back negative--also blood test---I finally found a celiac doctor whom my daughter recommended--she also has celiac disease--she did a cheek swap and sure enough I have celiac disease and have had it for a few years. I started having stomach problems and had a hernia and a sphincter that didn't close--so this was the problem with my severe bile reflux and gerd. I developed scurvy a year before that and it took 3 months for doctors and a specialist to try and find out what it was. I had it very badly on my whole right leg. Discolored-blood collections under the skin---the hundreds of red dots-due to very low platelets- All of the symptoms I had visible and not and no one put it together. I kept suggesting it was a problem with malnutrition but no one listened. My stomach and throat were raw. Had all kinds of tests done---finally my oncologist told me to have a leg biopsy done and sure enough it came back as scurvy. A lot of damage was done to my digestive system. Also had my gallbladder removed-had a small stone--they thought this might have been the source of the reflux --I ended up with worse reflux. It took me 2 years to find a surgeon to do the fundoplication--I am a high risk patient--allergic to many, many,drugs---pump prohibitors gave me seizures-so I am unable to take anything for the gerd. thought all would end there--I still have reflux severely---weigh 93 pounds with many food allergies--casein, yeast all dairy and it goes on----no rice-my blood counts and platelets are always bad--high calcium--cysts now found on my thyroid and most probe my parathyroid glands--didn't show any if the x-rays but I have all the symtoms-kidney stone--I only have one kidney--donated the other to my sister in 1968. I live in pain every day--trying to cope---your articles help me a lot. Thank you.

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    Guest European lady

    Posted

    I am a Northern European lady and have family history of gluten sensitivity, I am gluten sensitive but do not have DQ2 OR DQ8 AND had one doctor at Mayo clinic telling me that it is 100% certain that I can't have Celiac disease.

    A gluten-free diet put my intestinal symptoms on the right track.

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    Guest Mimi

    Posted

    Thank you for a novice friendly explanation of the genetic testing for celiac disease. I did not know about the alpha and beta-I only had one done.

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    Guest Linda Hays

    Posted

    It was very good and informative.

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    Guest Jean

    Posted

    Thank you for this article. It confirms suspicions that I had about family members in my family who probably have the disease and refuse to consider it. All members that I'm referring to have diabetes.

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    Guest LENA

    Posted

    I have a few concerns, I had a biopsy done in 10/08 and it tested negative for celiac disorder. However 7 months later I'm still having the same symptoms and now my doctor is saying that's not a guarantee (the biopsy) and there treating me as if I do have celiac now.

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  • About Me

    A practicing gastroenterologist in direct patient care but who also participates in teaching medical students and physicians in training as a Clinical Professor of Medicine at Rocky Vista University College of Osteopathic Medicine and at Kansas City University of Medicine and Biosciences. In addition to authoring peer review articles, book chapters and presenting clinical research Dr. Lewey has conducted, he has authored over 50 online articles, numerous blog posts and tweets about digestive and food related issues. As a physician who is a fellow of six professional societies Dr. Lewey serves at a national level on several committees, as a reviewer for journal articles and case reports, a media representative for the AOA Media and ACG on digestive health and disease and has been featured in various print, television, podcast and online media publications about digestive issues. As a expert in digestive diseases Dr. Lewey is also a medical legal consultant and expert witness. Dr. Lewey can be reached at Facebook.com/thefooddoc, on twitter @thefoodgutdoc and at www.thefooddoc.com, and his blog www.thefooddoc.blogspot.com.

  • Related Articles

    Jefferson Adams
    Celiac.com 06/26/2007 - Celiac disease is one of the most common chronic health disorders in western countries. It is also one of the most under-diagnosed. Up until ten years ago, medical schools taught that celiac disease was relatively rare and only affected about 1 in 2,500 people. It was also thought to be a disease that primarily affected children and young people. Recent studies and advances in diagnosis show that at least 3 million Americans, or about 1 in 133 people have celiac disease, but only 1-in-4,700 is ever diagnosed.
    The National Institutes of Health shows the prevalence of celiac disease to other well-known conditions as follows:
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    Scott Adams
    This article appeared in the Spring 2007 edition of Celiac.coms Scott-Free Newsletter.
    Celiac.com 08/29/2007 - The XII International Celiac Disease Symposium, proudly hosted by the Celiac Disease Center at Columbia University, featured presentations from researchers from all over the globe. The last session of the scientific portion of the symposium, entitled “Non-Dietary Therapies”, was full of controversy and fireworks. Talks given by Drs. Khosla, Gray, Paterson, Anderson and Mitea all revealed that potential alternatives to the gluten free diet are now being aggressively pursued. Several groups have even spun off from pharmaceutical companies to raise funds to test these alternatives in patient trials. However, several questions remain. How close are we to a “pill” or “vaccine” to treat or prevent celiac disease? And do we even need, or more importantly, WANT them, given that the diet is safe and effective?
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    In summary, some of these future potential treatments include:
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    Jennifer Arrington
    I would hate to add up all the hundreds of dollars I have wasted trying to get healthy.  Now, however, I get healthy by focusing on one thing:  making my intestines healthy.  If my intestines are healthy, I can absorb food.  If I can absorb food, my body will be receiving the nutrition it needs to function, and thus I will be healthy.
    Of course, rule number one for all of us is to stay gluten free.  But, focusing on avoidance alone, can get depressing.  Instead, I like to focus on what I can do to strengthen my digestive system.  That way, all the good gluten free food I am consuming can actually benefit my body.  What good is eating healthy if you are unable to absorb the nutrients?  Pouring healthy food into a compromised gut would be as wasteful as pouring dollar bills over an ATM machine and hoping in vain to strengthen your bank account balance.
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    Before I go on, I do want to say that the products listed below do not benefit me financially in the least.  Additionally, these are the products that work best for my body.  You may find a different brand works better for you, but as long as our focus is on getting those intestines healthy, we are all heading in the right direction!
    So, read on about what I personally consider the top four intestinal healing supplements…
    The first and best all-round product I have found that truly aids in restoring the intestinal lining is a glutamine supplement put out by a company called Metagenics.  The supplement, called “Glutagenics”, contains glutamine, licorice root, and aloe vera.  While studying for my masters in nutrition at Texas A&M University, we learned that glutamine is a key amino acid that aids in restoring the intestinal lining in patients that are transitioning from being tube-fed to a normal diet.   So, when my own chiropractor suggested this supplement and mentioned it contained glutamine, I purchased it and have been taking it on and off for three years.  
    Glutagenics is available online through various websites that carry the Metagenics brand. The supplement is unfortunately a bit cost prohibitive, but you can shop around for other brands that contain a similar blend, or buy the three active ingredients separately. Unfortunately, this did not work for me (I have an expensive gut), but it may for you.
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    Of the four products listed above, the two that I take daily are the probiotic and omega-3 oil. The other two I take on an ‘as-I-need-it’ basis.
    Unfortunately, our bodies don’t tolerate a lot of extra supplements, so go slowly and only add one at a time. Keep track of how you feel. You may never tolerate the mass quantities that some companies will try to sell you. But, since you are your own best manager, work with yourself slowly and patiently and you will find your health improves over time.
    May God bless you with the wisdom and discernment you need to live a healthy and vibrant life!


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