Do You Need Specific Genes to Have Gluten Sensitivity?

Unlike Celiac Disease, Gluten Sensitivity Doesn't Seem to Require Exact Genetics

Although research into non-celiac gluten sensitivity is just beginning and studies showing it's a distinct condition haven't yet been replicated, preliminary results indicate that you don't need to carry either of the so-called celiac disease genes in order to develop gluten sensitivity.

Those with celiac disease, the best understood of the five different types of gluten "allergy," almost always carry one of two very specific genes. In fact, doctors routinely use gene testing to rule out celiac disease — if you don't have the gene required to develop celiac, they say, you almost certainly don't have the condition.

The genetics of non-celiac gluten sensitivity is far less clear.

Illustration of strands of DNA
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How Genetics Plays a Role in Celiac Disease

The "celiac disease genes" appear in about 35 to 40% of the overall population, and the fact that you have the genes doesn't mean you'll necessarily develop celiac disease — it simply means you have the genetic potential to do so.

The genes that predispose you to celiac disease are known as the HLA-DQ genes, and they're found on the HLA-class II complex of our DNA. Everyone gets one copy of an HLA-DQ gene from their mother and a second copy of an HLA-DQ gene from their father.

There are four general types of HLA-DQ genes, known as HLA-DQ1, HLA-DQ2, HLA-DQ3, and HLA-DQ4. HLA-DQ1 is further broken down into HLA-DQ5 and HLA-DQ6, while HLA-DQ3 is further broken down into HLA-DQ7, HLA-DQ8, and HLA-DQ9.

Since everyone gets two HLA-DQ genes (one from their mother and one from their father), a person can have any one of many, many different gene combinations. Some of these genes predispose you to celiac disease, while preliminary research indicates other genes may predispose you to gluten sensitivity.

We know that the vast majority of people with biopsy-proven celiac disease carry either HLA-DQ2 or HLA-DQ8 (a subset of HLA-DQ3). However, since about 35% or 40% of the population carries one or both of those celiac disease genes, having the genes doesn't mean you'll definitely get celiac — there are other (mainly undiscovered) factors involved.

Genes Involved in Gluten Sensitivity

When it comes to gluten sensitivity, it appears that the celiac disease genes aren't much in play, according to some preliminary research.

In the gluten sensitivity research study released in early 2011 by University of Maryland celiac researcher Dr. Alessio Fasano, the authors analyzed the genes of those diagnosed with gluten sensitivity and compared them with another group of people who all had a so-called "gold standard" celiac disease diagnosis through blood tests and biopsy.

The researchers found that only 56% of those diagnosed as gluten-sensitive carried DQ2 or DQ8, indicating that those genes are far less involved in the development of gluten sensitivity than they are in the development of celiac disease. However, the genes did appear more often in those with gluten sensitivity than they do in the general population, so perhaps they may play some role in gluten sensitivity — it's just not clear what role they may play.

Of course, many physicians want to see Dr. Fasano's findings replicated before they agree that gluten sensitivity exists. Dr. Fasano currently is working to identify biomarkers that could lead to a test for gluten sensitivity.

Other Genes Potentially Involved in Gluten Intolerance

Dr. Kenneth Fine, who developed the EnteroLab gluten sensitivity testing process, says he believes that everyone with the genes HLA-DQ2 and HLA-DQ8 "will present gluten to the immune system for reaction — i.e., be gluten sensitive."

But those with HLA-DQ2 and HLA-DQ8 aren't alone in their gluten sensitivity, Dr. Fine says. He believes everyone with HLA-DQ1 and HLA-DQ3 also is predisposed to having gluten sensitivity. That means only people with two copies of HLA-DQ4 (less than 1% of the U.S. population) are immune from genetically induced gluten sensitivity, according to Dr. Fine. In his opinion, the rest have the genetic potential to develop the condition.

People with two copies of specific genes, such as HLA-DQ7 (a form of HLA-DQ3 that's similar to HLA-DQ8), risk very strong reactions to gluten, just as people with two copies of HLA-DQ2 can develop very severe celiac disease, he says.

Remember, Dr. Fine's research hasn't been replicated by others studying the genetics of celiac and gluten sensitivity, so it's not clear if it will be validated or not. However, if his predictions turn out to be accurate, that would mean almost everyone in the U.S. has some of the basic genes needed to develop gluten sensitivity. However, since not everyone does have the condition (see my article How Many People Have Gluten Sensitivity?), there must be other factors and genes involved.

The Bottom Line

Other researchers still need to confirm these preliminary results and hypotheses for them to be widely accepted in the medical community, and there's plenty of skepticism among physicians on whether gluten sensitivity exists at all. Based on all of this, gene testing for gluten sensitivity is unlikely to become helpful or practical in the real world at this time, if ever.

Still, both Dr. Fasano and Dr. Fine, among others, continue to study the issue of gluten sensitivity genetics. Their research indicates that even if your celiac gene test was negative, you still could have a problem with gluten.

EnteroLab fact sheet: Frequently Asked Questions About Results Interpretation

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  • A. Fasano et al. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Medicine 2011, 9:23.
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