Celiac Disease and HLA-DQ8 Gene

Celiac disease is an autoimmune disorder in which the eating of gluten can cause gastrointestinal symptoms and damage to small intestines. It is a disease which is still not fully understood but appears strongly linked in part to a person's genetics.

We know this from a broad perspective insofar as the risk of celiac disease increases significantly if a first-degree relative, such as a parent or sibling, also has the disease.

In recent years, with the advent of genetic testing, scientists have been able to identify two specific genes which appear more commonly in people with celiac disease. They belong to a group of gene complexes known as human leukocyte antigen (HLA) and include:

• HLA-DQ2, which is present in around 90 percent of people with celiac disease
• HLA-DQ8, which is seen in roughly eight percent of the same population

While HLA-DQ8 may seem a less compelling cause of the disorder, it accounts for the majority of non-DQ2 cases and has other characteristics that make it particularly striking.

There are many different types (serotypes) of the HLA-DQ genes of which DQ2 and DQ8 are only two. As a group, their main function is to help the body identify agents that may be harmful, allowing the immune system to target those cells for neutralization.

Every one of us has two copies of an HLA-DQ serotype, one which we inherit from our mother and the other which we inherit from our father. If a person inherits the same HLA-DQ type from their parents, he or she is said to be homozygous. If the person inherits two different types, that is referred to as being heterozygous.

As a unique serotype, HLA-DQ8 is most commonly linked to autoimmune diseases including celiac disease, rheumatoid arthritis, and juvenile diabetes. For reasons unknown, this gene can turn the body's defenses against itself, directing the immune system to attack and destroy its own cells.

With regards to celiac disease, research has suggested that being HLA-DQ8 homozygous increases your risk ten-fold compared to the general population. Even with one copy HLA-DQ8, your risk more than doubles.​

However, heterozygosity doesn't always mean less risk. If you combine HLA-DQ8 with a high-risk version of HLA-DQ2, your likelihood of the disease jumps to nearly 14 times that of the general public.

The expression HLA-DQ8 can vary significantly from one part of the world to the next. In Europe, for example, it is most associated celiac disease and juvenile diabetes. Similarly, in Japan, where this is no HLA-DQ2, the DQ8 serotype is the sole cause of celiac disease (bolstered, in part, by the influx of gluten in the Japanese diet).

By comparison, HLA-DQ8 represents only a small portion of the celiac disease cases in the U.S. and is more commonly associated with rheumatoid arthritis. Not that it matters in terms of disease progression. To date, there is no suggestion that either serotype has any impact on the severity of the disease. As such, it is likely that other factors play a part in why some people get the disease worse than others.