Coeliac disease is a genetically linked condition (through the Human Leukocyte Antigen (HLA) gene system) and clearly runs in families. However, having a relative with the condition (even a first degree relative like a brother, sister or parent) does not guarantee that you will ever develop the condition. In fact, the risk is low – around a 1 in 10 lifetime risk, that means a 90% chance of not developing the condition.
Here we answer some of your questions on genetics and coeliac disease:
What is an HLA gene?
Human Leukocyte Antigen (HLA) genes are often associated with certain conditions. They are also known as disease association genes or sometimes permissibility genes.
What is the HLA type associated with coeliac disease?
People with coeliac disease are known to have one of either HLA DQ 2.5 (commonest), HLA DQ8 (less common) or HLA DQ2.2 (least common). Put another way, having that genetic factor might mean that you will develop coeliac disease in your lifetime but it does not mean that you would definitely develop it.
What does the DQ positivity mean and how does it help cause coeliac disease?
In people with coeliac disease the DQ code on the cells (inflammatory T cells) in the lining of the gut (mucosa) recognise parts of the protein sequence of gluten (from wheat, barley and rye in the diet) and cause inappropriate inflammation – for people who don’t have coeliac disease this doesn’t happen. When someone with coeliac disease goes on a gluten free diet, those cells don’t seem to do anything, because they are not being stimulated and the inflammation doesn’t happen.
Could I have coeliac disease and not have one of those HLA types?
It would be rare for someone medically diagnosed with coeliac disease not to have one of these HLA types – it’s thought to be less than 1% and it’s because the other DQ types are so rare, it’s not cost effective to check for absolutely every one that’s been identified. That’s why a negative DQ typing result is very good, but not perfect, in ruling people out of risk categories.
What percentage of the general population have the coeliac disease genetic type?
Up to 40% of the general population also carry these DQ types - they are very common.
What happens to most of the people in the population with a positive DQ type?
Most people with the positive HLA-DQ type will never develop coeliac disease. There are other genes (not in the HLA system) that have been shown to be linked to coeliac disease and that are thought to be important in those who eventually develop the condition but we don't yet know their relevance.
What is an at risk group?
Guidance from BSPGHAN and NICE reports that certain groups are more likely than the general population to have coeliac disease. On average, around 1 in 20 (5%) of people in some at risk groups might develop the condition. It has been suggested that having the DQ type checked early on in a screening process might be helpful in some of those patients.
The BSPGHAN guideline states that DQ testing should be considered for patients who have Type I diabetes, selective IgA deficiency, Down's, Turner or Williams' syndromes, autoimmune thyroid and autoimmune liver disease, patients with unexplained raised liver enzymes and first degree relatives of people diagnosed with coeliac disease. The NICE guideline recommends these at risk groups are given blood tests for the antibodies associated with coeliac disease and does not recommend DQ testing in the initial diagnosis of coeliac disease in non specialist settings.
This is something you would discuss with your specialist as this is only guidance, and not a formal policy.
How do I get tested? Is it a test that I can get through my GP?
HLA-DQ typing is a test that is done in more specialist settings and advice is usually through the hospital teams dealing with patients with coeliac disease or with colleagues who follow at risk groups.
My child has Type 1 diabetes and has been told by our doctor that they should have the HLA-DQ test and if they are negative then they don't need further screening for coeliac disease - what are the chances of this?
The BSPGHAN guideline for the diagnosis and management of coeliac disease in children recommends children with Type 1 diabetes are tested for their HLA-DQ type. Since the publication of the guideline in 2013, there have been two studies (one from the Netherlands, the other from Scotland) which show that the chances of being negative for the DQ types associated with coeliac disease ie DQ2.5, DQ8 or DQ2.2 are less than 10%.
If first degree relatives of someone diagnosed with coeliac disease are tested for the associated DQ types it is likely only around 15% will be negative.
However, for children with Down's syndrome, the number we can take out of screening is much higher as around 50% will have a negative DQ test. For other at risk groups like Turner and Williams’ syndrome, thyroid disease and other at risk conditions, we currently do not know the real usefulness of DQ testing.
If a DQ type is positive, dependent on what the result is, it is possible to give a relative risk for developing coeliac disease, for example high, moderate or low.
I definitely don’t have coeliac disease but have been tested and told I am DQ 2 and 8 negative?
This is a very helpful result. A negative DQ type virtually excludes someone from having coeliac disease in their lifetime (less than 1% chance).
I definitely don’t have coeliac disease but I have been tested and it looks like I have the HLA-DQ genes? What’s my risk of developing the condition?
If you are positive for DQ 2.5, DQ 8 or DQ 2.2 it doesn’t actually diagnose you as having coeliac disease. It just means that you might one day develop the condition, and even then, the majority of people don’t. Remember, if an estimated 1% of the population has coeliac disease (1 in 100), that means there is a huge number of DQ positive people who do not have and will never have the condition. A positive DQ test does not, on its own, diagnose you as having coeliac disease.
Clearly if you have tested positive for HLA-DQ and have symptoms, the standard antibody blood test for coeliac disease is very important in helping make a diagnosis and you must continue to eat gluten during the testing process.
For those who are DQ positive and who want to know how much they are at risk, the chances of coeliac disease compared to the general population have been detailed as: highest risk is two copies of DQ 2.5, then one copy of DQ2.5 (high), followed by DQ8 (moderate) and DQ2.2 (lowest).
Clearly your risk is also determined by the rate of coeliac disease in any at risk group you may belong to (see earlier question on 'what is an at risk group?').
Some people who are positive for HLA-DQ will have reports that they have combinations of the DQ types, for example DQ2.5 / 8, DQ8 /2.2, etc. The reason for this is we potentially get two copies of the gene from our parents – those who have, for example two copies of DQ2.5, ie DQ2.5/2.5 are known as homozygous. If you just have one copy such as DQ2.5/- you are called heterozygous.
Remember, having the genetics does not mean that you have coeliac disease. For someone who doesn’t have the condition but feels compelled to have the test, the only really helpful DQ test is a negative one as that means you are very unlikely to ever develop coeliac disease.
I am already diagnosed with coeliac disease- should I be tested now or in the future at some point?
Currently there is no point in knowing your DQ type if you have coeliac disease as it will make no difference to what you do – gluten free living is the only proven treatment at this point in time.