Understanding the Genetics of Gluten Sensitivity

All of us have patterns of proteins on the surface ofwith microscopic or collagenous colitis, neurologic
our white blood cells. The proteins are known asmanifestations of gluten sensitivity and dermatitis
human leukocyte antigens (HLA), one of which is DQ.herpetiformis, which has been one of the gluten
Celiac Disease (CD) and non-Celiac gluten sensitivitysensitive conditions noted to be at times occurring in
(NCGS), and several autoimmune conditions occurDQ2, DQ8 negative individuals.
more frequently with certain HLA DQ types. DQWhy some people get Celiac Disease or become
gene testing is performed by analyzing cells from agluten sensitive is not wellunderstood. Certain factors
blood sample or from a Q-tip swab of the mouth.are believed to trigger it including the onset of
HLA types have a naming system that can bepuberty, pregnancy,stress, trauma or injury, surgery,
confusing even to scientist and physicians but here isviral or bacterial infections including those of thegut,
my explanation of the testing, the results, and whatmedication induced gut injury or toxicity e.g.
they may mean to you and your family.non-steroidal anti-inflammatorymedications such as
Each of us has two copies of HLA DQ. Becauseaspirin, ibuprofen, etc., immune suppression or
there are 9 serotypes of DQ we are all DQx/DQxautoimmunediseases. There is also a well known
where x is anumber between 1 & 9. Forgroup of individuals who are termed "latent" Celiacs.
example, I am DQ2/DQ7. I received the DQ2 fromThey are those at high risk because they have close
one of my parents and the DQ7 from the other.relatives who have Celiac disease with whom they
Because we get one DQ type from each of ourshare one or more of the Celiac genes DQ2 and/or
parents and give oneto each of our children it is easyDQ8. Though they usually have little or no symptoms
to to see how the DQ genes pass through a family.they may have abnormal blood tests and/or biopsies
This is important because two DQ types, DQ2 andindicating possible or definite Celiac disease. Others
DQ8, are estimated to be present in over 98% of allhave negative blood tests and normal biopsies but
people who have Celiac disease, the most severesymptoms that respond to a gluten-free diet.
form of gluten sensitivity.The severity of the sensitivity to gluten does appear
Rarely, true Celiac disease or dermatitis herpetiformis,to be related to the DQ type, family history (highest
the skin disease equivalent of Celiac, have beenrisk is in the non affected identical twin of a Celiac),
reported to occur in people who do not have DQ2pre-existing intestinalinjury, degree of exposure to
and/or DQ8. However, according to unpublished datagluten (how frequent and large a gluten load
from Dr. Ken Fine of Enterolab, the other six types,anindividual is exposed to), and immune status. Once
except DQ4, are associated with risk of elevatedinitiated, gluten sensitivitytends to be life long. True
stool antibodies to gliadin, the toxic fraction of gluten,Celiac disease does require lifelong complete gluten
and/or tissue transglutaminase (tTG) an enzyme.avoidance to reduce the increased risk of serious
Both of these antibodies are usually elevated in thecomplications such as severe malabsorption, cancers
blood of individuals with Celiac disease though they(especially of the GI tract) lymphoma, other
may be normal in the blood of individuals who areautoimmune diseases and premature death due to
gluten sensitive and have a normal small intestinethese complications.
biopsy but respond favorably to a gluten-free diet.Again, DQ testing can be done from cells from blood
Fine has publicly reported that elevated stoolor by a swab of the inside of the mouth but not all
antibodies to gliadin and/or tTG have been detectedlabs test for or report the full DQ typing but only the
in all of the untreated Celiacs tested in his lab, 60%presence or absence of DQ2 and DQ8. The lab that
of non-Celiacs who have symptoms consistent withperforms DQ testing is usually determined by an
gluten sensitivity, but in none of the controls testedindividual insurance company on the basis of
including cow manure. Follow up surveys of thosecontracts with specific commercial labs. However, if
individuals with elevated stool antibodies who initiatedyour insurance contracts with Quest Labs or the
a gluten-free diet compared with those with elevatedLaboratory at Bonfils (Denver, CO) full DQ can be
antibodies who did not reportedly showeddone if ordered and authorized by the insurance
significantly improved quality of life and symptoms incompany.
the gluten-free group.For those willing to pay out of pocket, Bonfils
He also reported DQ2 and DQ8 positive individuals,performs full DQ testing for Enterolab ( on a sample
have had as a rule the highest elevations of stoolobtained by a Q tip swab of the mouth. Since it is
gliadin antibody followed by those who are DQ7painless and non-invasive it is well tolerated especially
positive. Only those who are doubly positive for DQ4by young children. Also because the testing can be
have not been found to have significantly elevatedordered without a physician and the sample obtained
antibodies to indicate gluten sensitivity. This isin their home using a kit obtained from Enterolab it is
consistent with the differences in prevalence rates ofconvenient. The kit is returned by overnight delivery
Celiac disease seen in parts of the world. Since DQ4to Enterolab who forwards the test onto Bonfils. The
is not generally found in those of Caucasian race ofcost is $149 for the genetic testing alone and has to
Northern European ancestry, where Celiac incidence isbe paid for in advance by credit card or money order
highest, but in those from Asia or Southern Africaand is generally not reimbursed by insurance.
where there is a very low incidence of Celiac diseaseEnterolab also provides the stool testing for gliadin
and gluten intolerance.and tissue transglutaminase antibodies to determine if
DQ2 & DQ8, the two major types, are presentgluten sensitivity is evident. The gliadin antibody alone
in 90-99% of people who have Celiac disease. Theyis
are also present in approximately 35-45% of people$99 or the full genetic typing, stool testing for gluten
in the U.S., especially those of Caucasian race ofand cow's milk protein antibodies, and a test for
Northern European ancestry. The prevalence in theevidence of malabsorption is $349.
U.S. of Celiac disease is 1% and though a prevalenceAgain, the advantages of full DQ testing is to
of 1 in 100 is very common and much higher than haddetermine if someone has one or more copy of DQ2
been believed for years, this is only a fraction of theor DQ8 or carry both and therefore have a higher
genetically at risk that actually are confirmed to haverisk for Celiac disease or more severe gluten
Celiac disease by abnormal blood tests and smallintolerance. If you are DQ2 or DQ8 negative then
intestine biopsies. However, the number of peopleyour risk of Celiac disease is low, though not
who report a response to a gluten-free diet is muchnon-existent. If you are not DQ4/DQ4 then you do
higher.have a risk for gluten sensitivity. If you determine
Stool antibody test results would support this andthe full types within enough family members you can
the concept of a spectrum of gluten sensitivity thatpiece together a very accurate history of the origins
is much broader and in need of better diagnosticof Celiac and gluten sensitivity within a family and
definitions. I am an example of someone who is DQ2make some very accurate predictions of risks to
DQ7 who has normal blood tests for Celiac diseaseother family members.
but abnormal stool antibody tests and symptomsThough the lay public and many clinicians are finding
that have responded to a gluten-free diet. The strictthe genetic tests helpful, many, including most
criteria for diagnosis of Celiac disease by abnormalphysicians, do not understand the genetics of gluten
blood tests and a characteristic small intestine biopsysensitivity. We are awaiting Dr. Fine's published data
showing classic damage from gluten is much narroweron the significance of stool antibody tests and their
than what is being seen clinically.association to the other DQ types as his lab is the
It is becoming obvious to many of us who haveonly lab offering the stool antibody tests in the U.S.
personal and professional medical experience withOther Celiac researchers in U.S. have failed to
gluten intolerance and Celiac disease that the problemreproduce his assay but scattered reports in the
of gluten sensitivity is much greater and extendsliterature are appearing including a recent article in the
beyond the high risk Celiac genes DQ2 and DQ8.British Medical Journal indicating stool antibody testing
Traditionally it is reported and believed by many thatis feasible, non-invasive, and using their protocol,
if you are DQ2 and DQ8 negative you are unlikelytohighly specific but not sensitive for Celiac disease in
have Celiac disease or ever develop it. This cannotchildren.
be said with 100% certainty especially since there areIn the meantime, many patients are faced with
documented cases of Celiac disease and the skinwhether the failure of traditional blood tests, small
equivalent of CD, known as dermatitis herpetiformisbowel biopsies, and the presence or absence of DQ2
(DH), in individuals who are DQ2 and DQ8 negative.and DQ8 to diagnose or exclude gluten sensitivity
Knowing your DQ specific serotype pattern may bejustifies the uncertainty and added cost of full DQ
helpful for several reasons. If you have more thantesting and stool testing. Physicians unfamiliar with this
one copy of DQ2 or DQ8 you carry two of thetesting are increasingly being presented with the
major genes. For example if you are DQ2/DQ2, DQ2results and confused or skeptical pending published
DQ8, or DQ8/DQ8, a term Scott Adams of hasresults. There also continues to be a lack of
dubbed a "super celiac", you may be at much higherconsensus in the medical community regarding the
risk for Celiac disease and have more severe glutendefinitions of non-Celiac gluten sensitivity and what
sensitivity. Certainly if you are DQ2 and/or DQ8tests justify recommendations for gluten-free diet. It
positive you are at increased risk for Celiac disease.is clear though that gluten sensitivity by any criteria is
After a single copy of DQ2 or DQ8, it appears DQ7much more common than ever thought and a hidden
DQ7 might be next highest risk. Dr. Fine has alsoepidemic exists.
noted some other associations with the DQ patterns