CEN4GEN genetic testing

Celiac disease testing

CEN4GEN celiac genetic testing
What is celiac disease ?

Celiac disease is a medical condition, primarily affecting Caucasians, and is characterized by gluten sensitivity. It is also known as gluten intolerance, non-tropical sprue or gluten-induced enteropathy. Having celiac disease is permanent, and symptoms only manifest in predisposed individuals when exposed to dietary gluten. Gluten is a mixture of proteins present in cereal seeds like barley, oats, wheat and rye. In this mixture is a protein known as gliadin that is responsible for triggering the symptoms of celiac disease.

What are the symptoms of celiac disease ?

The symptoms of celiac disease vary in every predisposed person. The main symptoms may include bloating, abdominal cramping, flatulence, diarrhea, weight loss, decreased digestion and steatorrhea. Other atypical symptoms may include depression, headaches, mental confusion, fatigue, mouth ulcers, patchy hair loss, iron-deficiency anemia, constipation, skin problems like psoriasis, anxiety, autoimmune disorders, joint and muscle pain, numbness of leg or arm and so on.

The cause of celiac disease is multifactorial, meaning, its cause is dependent on the interactions of many factors such as genetic, environmental and immunological. However, in general the symptoms of celiac disease are triggered by the ingestion of gluten, aberrancies in the absorption of nutrients across the intestines, and having a genetic predisposition.

How is the diagnosis of celiac disease done ?

If you have symptoms of celiac disease, or if you have a family member who already has celiac disease, then it is recommended that you have a diagnostic test for celiac disease with an antibody screen blood test. This test initially involves the detection and quantification of antibodies to the tTG (Tissue Transglutaminase) and IgA markers in your blood.

If you are a child younger than 2 years, then testing for the Deamidated Gliadin antibody and IgG antibody blood markers should also be included. Depending on the results, testing for other antibodies to the Endomysial blood marker may be required. If you have celiac disease and you ingest gluten, the levels of these antibody blood markers will be significantly higher than normal levels, and the test result will be positive in about 98% of individuals who have celiac disease.

For healthy individuals without celiac disease, a negative test result will appear for 95%. Since these blood markers are produced by the immune system, someone who has celiac disease upon consuming gluten, induces an immune system response leading to the aberrant elevation in the levels of these blood markers. Therefore, you must be on a gluten containing diet in order to maximize the accuracy of this celiac disease diagnostic blood test. However, if you have a gluten free diet, it will cause ambiguous results in the celiac disease antibody screen test.

Therefore, it is important to discuss with your healthcare provider your dietary requirements for the gluten challenge, and whether you are a suitable candidate, prior to undertaking this diagnostic test. It must be noted that a false positive test result could emerge for someone with an existing medical condition and without having celiac disease. These individuals have an associated autoimmune disorders like autoimmune liver disease, Psoriatic or rheumatoid arthritis, Hashimoto’s thryoiditis, diabetes mellitus type 1, and so on. In conjunction, with the celiac disease antibody screen test, a follow up test that examines a biopsy of your small intestinal tissue is recommended for more definitive diagnosis.

Who needs to get diagnostic testing for celiac disease ?

You should discuss with your healthcare provider whether you are a suitable candidate to test for celiac disease and what are the diagnostic testing requirements. However, in general it is recommended for celiac disease diagnostic testing:

  • If you have symptoms of celiac disease, including children older than 3 years of age.
  • If you have a first degree relative who has already been diagnosed with celiac disease.
  • If you have an existing autoimmune disease or a disease associated with immune system problems, such as Williams syndrome, Turner syndrome, autoimmune thyroid disease, diabetes mellitus type 1, autoimmune liver disease, selective immunoglobulin A deficiency and so on.

Is celiac disease inherited ?

Celiac disease is not inherited, but the susceptibility to developing celiac disease is inherited. The risk for developing celiac disease is influenced primarily by the human leukocyte antigen genes: HLA-DQA1 and HLA-DQB1. Specific mutations in the HLA-DQA1 gene results in the HLA-DQ2 genetic marker, while specific mutations in the HLA-DQB1 gene results in the HLA-DQ8 genetic marker.

The human leukocyte antigens function in the immune system to help the body distinguish between entities that are part of the body, and those that are considered foreign entities or entities that have been introduced to the body such as microorganisms or things that are consumed such as from the diet. There could be other non-human leukocyte antigen genes involved, but more medical research is needed to establish the roles of such genes with celiac disease.

More than 98% of patients with celiac disease have a specific type of mutation either in the HLA-DQ2 and/or HLA-DQ8 genetic markers. Therefore, genetic testing / DNA testing is important to identify these genetic markers in a person and to help establish the status of genetic predisposition to celiac disease. However, it must be noted that up to 40% of the general population also have these genetic marker mutations and never develop celiac disease.

Genetic testing / DNA testing for the detection of the HLA -DQ2 and/or HLA-DQ8 genetic markers, is not used to diagnose you with celiac disease. However, if Genetic testing / DNA testing uncovers that you carry the HLA-DQ2 and/or HLA-DQ8 genetic marker mutations, your risk for developing celiac disease increases to 3%, when compared to the general population risk of less than 1% for developing celiac disease and without having these specific genetic marker mutations.

It could be for those who develop celiac disease, these genetic marker mutations may imply other complex factors like the environment that could corroborate in increasing the risk. Most remarkable, individuals who have both HLA-DQ2 and HLA-DQ8 genetic mutations are most likely to develop celiac disease than those having only the HLA-DQ8 genetic mutation, but the risk is the same compared to those with having only the HLA-DQ2 genetic mutation. There is no difference in the severity of symptoms between individuals who have only the HLA-DQ2 or only the HLA-DQ8 genetic mutations, but individuals with only the HLA-DQ2 genetic mutation have a higher risk for developing celiac disease than those having only the HLA-DQ8 genetic mutation.

Since the susceptibility to developing celiac disease is genetic, Genetic testing / DNA testing can be used to infer the risks of other family members for developing celiac disease. For instance, if your first degree family member such as your child, sibling, and parent shares the same HLA-DQ2 and/or HLA-DQ8 genetic mutations as a family member with celiac disease, your family member has a 10 to 40% risk of also developing celiac disease. This is significantly higher, when the overall risk for developing celiac disease is less than 1% when the HLA-DQ2 and/or HLA-DQ8 genetic mutations are absent.

A negative result obtained from genetic testing / DNA testing of a first degree family member implies that the possibility for those related family members to develop celiac disease can be excluded. Genetic testing / DNA testing for the susceptibility to develop celiac disease is important and recommended for family members, especially children, of those individuals who already have celiac disease. First degree family members identified with positive results of the HLA-DQ2 and/or HLA-DQ8 genetic mutations are recommended to be screened for celiac disease every 3 to 5 years.

Who needs to get genetic testing / DNA testing for celiac disease predisposition ?

Celiac disease screen with a panel of antibody markers is used to diagnose celiac disease. However, for those individuals who are on a gluten free diet, it may obscure the accuracy of the celiac disease antibody blood test. Therefore, genetic testing / DNA testing for celiac disease predisposition is recommended under the following scenarios:

  • To test your other family members if you already have celiac disease. A negative genetic test / DNA test result will imply there is a 99% chance that your family member will not develop celiac disease. A positive genetic test / DNA test result will imply that your family member has increased risk of developing celiac disease and should be diagnostically screened for celiac disease every 2 to 3 years, or immediately if symptoms of celiac disease appear.
  • To resolve the uncertainty in the diagnosis of celiac disease, or ambiguous/conflicting results obtained from the celiac disease antibody screen, as well as from small intestinal biopsy examinations.

At CEN4GEN, we offer both celiac disease antibody based diagnostic testing, as well as DNA testing / genetic testing for determining the susceptibility of developing celiac disease. To learn more about how our testing options can suit your needs, contact us at contact@cen4gen.org, and a representative will guide you through the testing process and provide more information for you and your healthcare provider.

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