Celiac genes

The short answer is yes, celiac disease can be ruled out >99.0% of the time in this case.1 Negative tests for both HLA-DQ2 and HLA-DQ8 genes make celiac disease highly unlikely.

Here’s why:

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“HLA-DQ2 and HLA-DQ8 are the names of two genetic markers which are part of the immune system and are able to stick to the gluten proteins. Every person with celiac disease has at least one of these genetic markers. If your doctor is unsure as to whether or not you have celiac disease, s/he can perform a simple blood test to determine whether or not you have one or both of these genes. If you do not have one of these two genetic markers, your doctor can rule out celiac disease [with ~99% certainty]. If you DO have one of these genetic markers, it is possible that you have or may develop celiac disease in the future. Your doctor will need to perform more tests. You do NOT need to eat gluten in order to have the gene testing.”2 [Text added by Melinda Dennis]

And a little more detail about the genes:“The Human Leukocyte Antigen (HLA) genes are linked to many autoimmune diseases such as celiac disease. Everyone has a copy from the mother and a copy from the father. These copies can come in different versions called alleles. The HLA gene alleles that predispose a person to celiac disease are called DQ2 and DQ8. One may have DQ2 or DQ8 in one of the copies or in both. People who have only one copy of DQ2 or DQ8 have a risk of about 3% of having celiac disease, whereas people who have two copies of either have a risk ~10%. Rarely, people with only 1/2 of the DQ2 gene can get celiac disease but this occurs in <5% of people with celiac disease.

HLA types are actually combinations of genes so it is possible to be DQ2 positive even if neither of your parents has this gene. Overall though, at least 50% of children of parents carrying DQ2 or DQ8 will also have one of these. Almost all people with celiac disease have at least one DQ2 or DQ8 copy. This is why genetic testing is so useful to rule out celiac disease. Nevertheless, since 30-40% of the general population has at least one copy of DQ2 or DQ8, the gene test is not a good test to confirm celiac disease.”2

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A couple of take-away points:

1. Genetic testing can only be used to rule out celiac disease but will not definitively confirm it. If you think you might have celiac disease and you HAVE one of the genetic markers, your doctor will need to perform more tests.
2. If a person has already started a gluten-free diet based on a presumed diagnosis of celiac disease, his/her doctor will recommend the genetic testing to help rule-out the possibility of celiac disease. This is because genes do not change during one’s lifetime so a person’s diet will not affect the testing in any way.

Read about other conditions where HLA-DQ2 and HLA-DQ8 genetic testing can be valuable.

1. CeliacNow.org. Genetics – Level 2. https://www.bidmc.org/-/media/files/beth-israel-org/centers-and-departments/digestive-disease-center/celiac-center/genetics_level2.ashx?la=en&hash=CDD9D4C1E804CFBA48F64CD4042CD0853D79C3E3
2. CeliacNow.org. FAQ:Diagnosing Celiac Disease. https://www.bidmc.org/-/media/files/beth-israel-org/centers-and-departments/digestive-disease-center/celiac-center/2faq-diagnosing-celiac-disease-feb-2016.ashx?la=en&hash=14EEDD7CF8431C4B098941F697DCD8F6E97901B2. Scroll to bullet points #12-13.

Reviewed and updated October 4, 2022.

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