The Genetics of Gluten Sensitivity

In recent years gluten free diets have become very popular. Despite the fact that more and more people are eliminating gluten from their diets, the science remains somewhat unclear.

This post aims to demystify the genetic basis of gluten sensitivity. First of all, what is gluten? Gluten is the general name for two proteins (gliadin and glutenin) that can be found in wheat, rye and barley. Gluten acts to maintain the shape of these cereals, by working as the glue that holds them together. Gluten can trigger various different reactions in people with sensitivities. Here we will focus on 3 general classes of sensitivity, coeliac disease, wheat allergy and non-coeliac-gluten-sensitivity.

Coeliac (or celiac) disease is arguably the most serious of the three. It is an autoimmune disease, which means that eating gluten triggers the body’s own immune system to attack the small intestine. This response causes symptoms affecting multiple systems including unexplained gastrointestinal symptoms, tiredness and even depression. Prolonged exposure to gluten through continuing to eat cereals leads to permanent damage to the small intestine, and ultimately reduces its ability to absorb nutrients. Coeliac disease is reasonably rare, affecting approximately 1% of Western populations. There is no cure and the only treatment is to completely eliminate gluten from the diet. It is possible to test for coeliac disease through DNA testing as certain mutations in genes involved in the immune system (such as MYO9B and HLA-DRB) act as markers for the disease.

Wheat allergy is an antibody based reaction to the ‘gliadin’ component of wheat. Symptoms are similar to other common allergies and include an itchy mouth, nose, eyes and throat, skin rash and wheezing, and difficulty breathing. Sufferers may also experience gastrointestinal symptoms similar to coeliac disease, however these do not cause permanent damage to the small intestine. This disorder tends to run in families, so children with two parents that suffer from various allergies are the more likely to have a wheat allergy. According to American statistics 0.4% of children are allergic to wheat. However, 70% of children will grow out of their allergy by age 14. It is possible to test for a wheat allergy through blood testing, which detects antibodies against wheat in the body, or using a skin prick test, which is a common method of screening for many different allergies.

Unfortunately the third category is much less clear cut. Non-coeliac-gluten-sensitivity (NCGS) is a condition where symptoms are experienced following gluten consumption in patients where both coeliac disease and wheat allergy have been ruled out. Symptoms include gastrointestinal issues but extend to behaviour disturbances and systemic manifestations (such as anaemia and muscle pain). Determining an exact cause for this condition has proven difficult, as possible candidates in animal studies did not cross over well to humans. Further, those studies carried out on humans have been flawed as a result of small sample sizes and inconsistent protocols. One suggestion that is clear across the literature is that there are many similarities between gluten sensitivity and sensitivity to special sugars known as FODMAPs, and sufferers of NCGS often benefit from limiting their intake of high FODMAP containing foods. As a result of the unclear scientific basis it is not possible to take a test for this condition, however many people seem to benefit from working with a nutritionist to develop a diet that works for them based on trial and error.

So why is it important to get testing done? Coeliac disease is a serious immunological disease and as there is no cure, early diagnosis and changing to a gluten free diet is crucial to avoid permanent damage to the GI tract. It also has a genetic basis and can thus be passed down through generations, so knowing that a parent has coeliac may enable early diagnosis in their children. Wheat allergies can also be life threatening, and are very easy to test for. NCGS is a difficult condition to describe but ruling out both coeliac and wheat allergies is an important first step, and a huge amount of research is going into this area to enable a better characterisation in future. On the other hand it is important to note research has shown that non-coeliac athletes experience no improvement to either exercise performance or physiological factors through short term switching to a gluten free diet. Eliminating an entire food group from your diet without medical advice can lead to deficiencies in important dietary elements if the right replacements are not made.

The rise in gluten based sensitivities in recent years is interesting because it shows how a tightly regulated biological system can end up in serious trouble as the result of a few tiny mutations. Advances in modern genetics have already allowed definitive DNA based testing for diseases such as coeliac and many others. Here at AthGene we think diagnosis of diseases through genetic testing is the future, and we are excited to see what is next for this fascinating field of science.

References:

• Michael Pollan’s Netflix Series “Cooked” — Season 1 Episode 4: “Air”
• www.calorielab.com/news/2011/01/01/big-8-food-allergies/
• Lis, D., Stellingwerff, T., Kitic, C. M., Ahuja, K. D., & Fell, J. (2015). No Effects of a Short-Term Gluten-free Diet on Performance in Nonceliac Athletes. Medicine & Science in Sports & Exercise, 47(12), 2563–2570.
• Thomas, J. R., & Nanda, F. (2012). A FODMAP Diet Update: Craze or Credible?. Practical Gastroenterology, 1(5), 4.
• Biesiekierski, J. R., & Iven, J. (2015). Non-coeliac gluten sensitivity: piecing the puzzle together. United European Gastroenterology Journal, 3(2), 160–165.

Genetics. Gluten. Celiac. Coeliac. Intolerance. Genes. MYO9B. HLA-DRB. Gluten Free Diet.