HLA-DQ2: The Primary Celiac Disease Gene

definition of celiac disease
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Celiac disease is a genetic condition, which means you need to have the "right" genes to develop it and be diagnosed with it. HLA-DQ2 is one of two main celiac disease genes, and happens to be the most common gene implicated in celiac disease (HLA-DQ8 is the other so-called "celiac gene").

Most doctors believe you need at least one copy of either HLA-DQ2 or HLA-DQ8 to develop celiac disease. 

Celiac Genetics Basics

Genetics can be a confusing subject, and the genetics of celiac disease are especially confusing. Here's a somewhat simplified explanation.

Everyone has HLA-DQ genes. In fact, everyone inherits two copies of HLA-DQ genes — one from their mother and one from their father. There are many different types of HLA-DQ genes, including HLA-DQ2, HLA-DQ8, HLA-DQ7, HLA-DQ9 and HLA-DQ1.

It's the HLA-DQ2 and HLA-DQ8 gene variants that raise your risk of having celiac disease.

Since everyone inherits two HLA-DQ genes (one from each parent), It's possible for a person to have one copy of HLA-DQ2 (often written as HLA-DQ2 heterozygous), two copies of HLA-DQ2 (HLA-DQ2 homozygous), or no copies of HLA-DQ2 (HLA-DQ2 negative).

In addition, there are at least three different versions of the HLA-DQ2 gene. One, known as HLA-DQ2.5, confers the highest risk for celiac disease; about 13% of Caucasian residents of the U.S. carry this specific gene. However, people with other versions of HLA-DQ2 also are at risk for celiac disease.

If You Have the Gene, What's Your Risk?

That depends.

People who have two copies of HLA-DQ2 (a very small percentage of the population) carry the highest overall risk for celiac disease. According to a proprietary risk estimate based on published research that was developed by genetic testing service MyCeliacID, celiac disease occurs in people with two copies of DQ2 at a rate around 31 times that of the general population.

People who have two copies of HLA-DQ2 also have an increased risk for at least one type of refractory celiac disease (which occurs when the gluten-free diet doesn't seem to work to control the condition), and for enteropathy-associated T-cell lymphoma, a type of cancer that's associated with celiac disease.

People who have only one copy of HLA-DQ2 have about 10 times the "normal population" risk for celiac disease, according to MyCeliacID. Those who carry both HLA-DQ2 and HLA-DQ8, the other celiac disease gene, have about 14 times the "normal population" risk.

Other Factors Are Involved

Not everyone who carries HLA-DQ2 develops celiac disease — the gene is present in more than 30% of the U.S. population (mainly those with northern European genetic heritage), but only about 1% of Americans actually have celiac disease.

Researchers believe there are multiple other genes involved in determining if someone who's genetically susceptible actually develops the condition, but they haven't yet identified all the genes involved.

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Article Sources

  • MyCeliacID Risk Stratification Table.

  • Al-Toma A. et al. Human Leukocyte Antigen–DQ2 Homozygosity and the Development of Refractory Celiac Disease and Enteropathy- Associated T-Cell Lymphoma. Clinical Gastroenterology and Hepatology. 2006 Mar;4(3):315-9.
  • Ploski R. et al. On the HLA-DQ(alpha 1*0501, beta 1*0201)-associated susceptibility in celiac disease: a possible gene dosage effect of DQB1*0201. Tissue Antigens. 1993 Apr;41(4):173-7.
  • Vader W. et al. The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses. Proceedings of the National Academy of Sciences. 2003 October 14; 100(21): 12390–12395.