Celiac Genetic Tests Are Not All Equal and Some DQ2 Negatives May Not Be Completely Negative

Genetic tests exist for Celiac disease and are highlyThe most commonly used laboratories for celiac
accurate for determining the risk of the disease.disease genetic testing in the U.S. are Kimball
When a complete genetic panel is performed theGenetics, LabCorp, Quest, Prometheus, and Enterolab.
possibility that someone having or ever getting thisThe Laboratory at Bonfils in Denver not only
autoimmune disease can be determined to anprovides testing directly but also does the testing for
extremely high degree of certainty. Unfortunately,several hospitals, Quest and Enterolab. Bonfils only
some tests are misleading because they do notdoes beta subunit testing. They report results of
include a portion of the genetic pattern that may beDQ2 and DQ8 negative based on the absence of the
present that can predispose to this gluten sensitivitybeta subunits associated with DQ2 and DQ8.
disease though the report may imply absence ofHowever this is somewhat misleading since someone
increased risk.could have only the alpha subunit and be "partially"
Some genetic tests can be done without a doctor'sDQ2.
order. Insurance coverage for the Celiac genetics isThough the risk of being "half" DQ2 positive from
highly variable. A couple of laboratories can run theonly having the alpha subunit is low overall it is still
tests on samples obtained from a mouth swab thatthere. Furthermore, there are people who may
is painless and well accepted by children. Geneticbelieve that they are DQ2 or DQ8 negative based on
testing can be done at any age while blood tests fortesting from Bonfils, Quest or Enterolab. These
Celiac are not recommended before a year of age.people and/or their doctor may exclude the possibility
Celiac genetic tests are not affected by eating glutenthat they have or are at risk for ever getting Celiac
or not.disease when in fact this may or may not be true.
If you do not have the commonly recognized HLAThe existence of DQ2 and DQ8 negative Celiac
genetic patterns DQ2 or DQ8 that are associateddisease has been debated. It is probably clouded to
with Celiac disease you are believed to not be at risksome degree by this confusion about the genetics.
for the full autoimmune disease. You don't need toMost experts assert that the presence of DQ2 or
be periodically retested. However, you still could beDQ8 is a requirement to develop the disease and
intolerant or sensitive to gluten. Knowing yourtheir absence excludes the possibility. However,
genetics can be very helpful if you have a familyreports of DQ2 and DQ8 negative Celiac disease
member with Celiac disease or they or you havepersist.
other autoimmune diseases associated with a risk ofI have a couple of patients who have the positive
Celiac.results for the specific blood tests for CD,
HLA DQ2 and DQ8 are the simple designations forendomysial or tissue transglutaminase antibody; and
complex white blood cell patterns or types that areclassic biopsy features but were reported DQ2 and
known to be associated with an increase risk ofDQ8 negative by laboratories who only test for the
Celiac disease. The HLA term stands for humanbeta subunit. Ideally, they should be re-testing for
leukocyte antigen. Leukocytes are white blood cells.alpha unit positive "half" DQ2 or DQ8 but this will
Antigens are proteins that serve or elicit an immunedepend on their insurance coverage. In the meantime,
response by the body. So, the HLA system is aI am remain concerned that many patients and
complex set of proteins on the surface of whitedoctors may be lulled into a false sense of security
blood cells. Everyone has two copies of a DQ proteinby negative genetic tests incompletely done or that
pattern. You get one copy of DQ from your momdiagnoses of Celiac disease may be or have been
and one from your dad. Having at least one copy ofwithdrawn on some individuals based on incomplete
either is necessary and sufficient to develop thegenetic results.
disease. Having two copies of either or one of bothThis issue of DQ2 and DQ8 testing is further
increases the risk even more.complicated by reviews on the subject that are
These protein patterns are inherited just like the redincomplete or vague. The best reviews I have found
blood cell proteins that constitute what is commonlyare by Ludvig Sollid and Benedicte Lie of Oslo,
known your "blood type". I, for example, am ANorway "Celiac Genetics: Current Concepts and
positive blood type. This means I have a pattern ofPractical Applications" Clinical Gastroenterology and
proteins designated A and Rh+ on the surface of myHepatology 2005 and Bourgey's 2007 review. In a
red blood cells. On the other hand I have a whiterecent update article by Victorien, there is a general
blood cell type pattern DQ2/DQ7 inherited from myreview the genetics of celiac disease including the
parents. My Dad gave me a DQ2 and my Mom theassociation of myosin IXB gene (MYO9B). However,
DQ7. You have two DQ patterns on your whiteit doesn't explain the DQ2 or DQ8 typing well. They
blood cells that you received from your parents andconclude that "To date, only HLA-DQ2 or HLA-DQ8
you give one of your DQ types to each of yourtyping is clinically relevant..." but fail to point out that
children.HLA DQ2 and DQ8 typing should include both alpha
Since only a single copy of either DQ2 or DQ8 can beand beta subunits.
associated with an increase risk of developing CeliacIt is clear that both HLA and non-HLA genetic factors
disease, most laboratories test for the presence ofare important in the risk of Celiac disease. However,
either and simply report their presence or absence.the absence of the high-risk genes does not preclude
However, knowing if you have one or two copiesadverse reactions to gluten including leaky gut, skin,
not only provides additional information about degreedigestive and neurological symptoms. When genetic
of your risk. It also may predict the severity. It alsotesting is used to try to assess the risk or exclude
provides information about your parents and yourCD then I recommend that full testing including both
childrens' risk of inheriting an at risk gene. If you havealpha and beta subunit typing. Hopefully more
DQ2 and DQ8 we know your complete DQ pattern.research will better define the genetics of both Celiac
We also known one of your parents had at leastdisease as well as non-celiac gluten sensitivity or the
DQ2 and the other DQ8. All of your children will eitherso called "gluten syndrome".
get a DQ2 or a DQ8. So, both your parents and all ofSelected References:
your children are at risk for Celiac in that situation. IfBourgey, M et al. HLA related genetic risk for Coeliac
you have only copy of DQ2 or DQ8 then we onlydisease. Gut 2007; 56:1054-1059.
know that at least one of your parents had oneJohnson, TC et al. Relationship of HLA-DQ8 and
copy of the risk gene and each of your children willseverity of Celiac disease: Comparison of New York
have a 50-50 chance of inheriting such a risk geneand Parisian cohorts. Clin Gastroenterol Hep 2004;
from you.2:888-894.
Other non-HLA genetic factors are involved in theKaukinen K. et al. HLA-DQ typing in the diagnosis of
risk of celiac disease. These are still being workedCeliac disease. Am J Gastroenterol 2002; 97(3):
out. However, one poorly understood and little695-699.
known fact to most doctors and almost all patients isLundin, KE. HLA-DQ8 as an Ir gene in Coeliac disease.
that HLA DQ2 and DQ8 testing done by someGut 2003; 52:7-8
laboratories does not include the full spectrum of atMazzarella G. et al. An immunodominant DQ8
risk components of these patterns. DQ2 and DQ8restricted gliadin peptide activates small intestine
are a summary blood type designations or serotypesimmune response in in vitro cultured mucosa from
for the presence of several protein subunits. ThereHLA-DQ8 positive but not HLA-DQ8 negative Coeliac
are alpha and beta subunits to these protein patterns.patients. Gut 2003; 52:57-62.
The beta subunit is the most influential and importantSollid, LM and Lie, BA. Celiac disease genetics: Current
component. Most laboratories only test for andconcepts and practical applications. Clin Gastro Hep
report the beta subunit. However, the alpha subunit2005; 3:843-851.
does carry risk on its own, albeit much less than theWolters,VM and Wijenga C. Genetic background of
presence of the beta subunit or the presence ofceliac disease and its clinical applications. Am J
both alpha and beta subunit.Gastroenterol 2008; 103:190-195.