Genetics

Celiac disease is a genetically linked condition (through the human leukocyte antigen (HLA) gene system). However, having a relative with the condition (such as a sibling or parent) does not guarantee that you will develop the disease. In fact, the risk is low – about 1 in 10, meaning there is a 90% chance that the disease will not develop.

What is the HLA gene?

Human leukocyte antigen (HLA) genes are often associated with certain conditions. They are also known as disease-associated genes. Human leukocyte antigens (HLA) are proteins that act as “markers” by binding to fragments of other proteins and signaling T-cells on how to interact with them. Defective HLA proteins bind to gluten fragments and mistakenly signal T-cells that these are bacteria or viruses.

What type of HLA is associated with celiac disease?

People with celiac disease are known to have HLA DQ 2.5 (the most common), HLA DQ8 (less common), or HLA DQ2.2 (the rarest). In other words, having this genetic factor may mean that you could develop celiac disease in your lifetime, but it does not necessarily mean that you will.

What does DQ positivity mean and how does it contribute to celiac disease?

In people with celiac disease, the DQ code on the cells (inflammatory T-cells) in the intestinal lining recognizes parts of the gluten protein sequence (from wheat, barley, and rye) and triggers inflammation – something that does not happen in people without celiac disease. When a person with celiac disease follows a gluten-free diet, these cells remain inactive because they are not stimulated, and inflammation does not occur.

Can I have celiac disease without having one of the HLA types?

It would be rare for someone diagnosed with celiac disease not to have one of these HLA types. It is estimated to be less than 1%, as other DQ types are very uncommon.

What percentage of the general population has the genetic type associated with celiac disease?

Up to 40% of the general population carry these DQ types – they are very common.

What happens to most people in the population with a positive DQ type?

Most people with a positive HLA-DQ type will never develop celiac disease. There are other genes (outside the HLA system) that have been proven to be associated with celiac disease and are considered important for those who eventually develop the condition, but their exact relevance is still unknown.

What is a risk group?

Certain groups are more likely than the general population to have celiac disease. On average, about 1 in 20 (5%) people in risk groups may develop the disease. It is suggested that checking the DQ type early in screening may be useful for some of these patients.

Blood tests for celiac-associated antibodies are recommended for patients with type 1 diabetes, selective IgA deficiency, Down, Turner, or Williams syndromes, thyroid disorders, liver disease, unexplained liver enzymes, and pancreatitis.

How can I get tested for celiac disease? 

The HLA-DQ test is performed in more specialized hospitals and laboratories, and consultations are usually conducted by hospital teams that deal with celiac patients.

My child has type 1 diabetes, and our doctor has said that an HLA-DQ test should be done, and if it is negative, then no further screening for celiac disease is needed – what are the chances of that?

Guidelines for diagnosing and treating children recommend that children with type 1 diabetes be tested for their HLA-DQ type. Studies show that the chances of being negative for the DQ types associated with celiac disease, i.e., DQ2.5, DQ8, or DQ2.2, are less than 10%.

If first-degree relatives of a person diagnosed with celiac disease are tested for the associated DQ types, about 15% are likely to be negative.

However, in children with Down syndrome, the number who can be excluded from screening is much higher, as around 50% will test negative for DQ. For other risk groups such as Turner and Williams syndromes, thyroid disease, and other risk conditions, the true benefit of DQ testing is currently unknown.

If the DQ type is positive, depending on the result, a relative risk for developing celiac disease may be provided, such as high, moderate, or low.

I definitely don’t have celiac disease, but I was tested and told I am DQ 2 and 8 negative?

This is a very useful result. A negative DQ type virtually excludes the possibility of having celiac disease for life (less than 1% probability).

I definitely don’t have celiac disease, but I was tested and it looks like I have the HLA-DQ genes? What is my risk of developing the condition?

If you are positive for DQ 2.5, DQ 8, or DQ 2.2, it does not actually diagnose you with celiac disease. It simply means that you may develop the condition one day, and even then, most people do not. Remember that if approximately 1% of the population has celiac disease (1 in 100), this means there are a huge number of DQ-positive people who do not and will never have the condition. A positive DQ test cannot, by itself, diagnose you with a celiac-related disease.

Очевидно е, че ако имате положителен тест за HLA-DQ и имате симптоми, стандартният кръвен тест за антитела за цьолиакия е много важен за диагностицирането и трябва да продължите да ядете глутен по време на теста.

За тези, които са DQ позитивни и които искат да знаят колко са изложени на риск, шансовете за цьолиакия в сравнение с общата популация са подробно описани като: най-висок риск са две копия на DQ 2.5, след това едно копие на DQ2.5 (висока), следвана от DQ8 (умерена) и DQ2.2 (най-ниска).

Ясно е, че рискът Ви се определя и от честотата на заболяването на цьолиакия във всяка рискова група, в която може да принадлежите.

Някои хора, които са положителни за HLA-DQ, ще имат комбинации от типове DQ, например DQ2.5 / 8, DQ8 /2.2 и т.н. Причината за това е потенциално да се получат две копия на гена от родители – тези, които имат например две копия на DQ2.5, т.е. DQ2.5 / 2.5 са известни като хомозиготни. Ако имате само едно копие като DQ2.5 / – Вие се наричате хетерозиготни.

Не забравяйте, че генетиката не означава, че имате цьолиакия. За някой, който няма състояние, но се чувства принуден да направи теста, единственият наистина полезен тест за DQ е отрицателен, тъй като това означава, че е много малко вероятно да развиете болестта.

I am already diagnosed with celiac disease – should I be tested now or at some point in the future?

There is currently no point in knowing your DQ type if you have celiac disease, as it will not affect what you do – a gluten-free lifestyle is the only proven treatment at this time.