HLA-DQA1

At least two specific combinations of HLA gene variants (HLA haplotypes) have been found to increase the risk of developing celiac disease, a disorder in which inflammation damages the intestinal tract and other organs and tissues. One of these haplotypes, known as DQ2, is composed of the protein produced from HLA-DQA1 gene variants known as HLA-DQA1*05:01 or HLA-DQA1*05:05 bound to the protein produced from HLA-DQB1 gene variants known as HLA-DQB1*02:01 or HLA-DQB1*02:02. The other haplotype, known as DQ8, is composed of the protein produced from HLA-DQA1 gene variants known as HLA-DQA1*03:01 or HLA-DQA1*03:02 bound to the protein produced from the HLA-DQB1 gene variant known as HLA-DQB1*03:02.

The DQ2 and DQ8 haplotypes, which may occur separately or together, seem to increase the risk of an inappropriate immune response to the protein gluten, which is found in wheat, rye, and barley. This immune system malfunction results in the damage to the body's organs and tissues that occurs in celiac disease. However, the DQ2 and DQ8 haplotypes are also found in 30 percent of the general population, and only 3 percent of individuals with these haplotypes develop celiac disease.

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Combinations of variations in the HLA-DQA1 gene and other HLA genes affect the risk of type 1 diabetes. Type 1 diabetes is characterized by high blood sugar (glucose) levels resulting from a shortage of the hormone insulin and is caused by autoimmune damage to insulin-producing cells in the pancreas.

Type 1 diabetes risk is most increased by two HLA haplotypes involving variations of the HLA-DQA1 and HLA-DQB1 genes and another HLA gene called HLA-DRB1. One haplotype, written as DRB1*03:01-DQA1*05:01-DQB1*02, is called DR3. The other haplotype, written as DRB1*04:01/02/04/05/08-DQA1*03:01-DQB1*02, is called DR4. People at highest risk of developing type 1 diabetes have one copy of the DR3 haplotype and one copy of the DR4 haplotype in each cell. Other HLA haplotypes only mildly increase the risk of type 1 diabetes, while some haplotypes seem to protect against developing this condition. Variations in other genes and environmental factors are also thought to affect the risk of this complex disorder.

Certain normal variations of the HLA-DQA1 gene have been associated with increased risk of autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs. It is unclear how different versions of the HLA-DQA1 gene influence the risk of developing autoimmune disorders. These conditions are thought to result from a combination of multiple environmental and genetic factors. Changes in other HLA and non-HLA genes, some of which remain unknown, also likely contribute to the risk of developing these complex conditions.

Normal variations in the HLA-DQA1 gene can affect the body's ability to recognize and react to foreign invaders (pathogens). For example, variations of this gene have been shown to increase or decrease a person's chance of getting infections such as hepatitis B and leprosy or may affect the severity of illness if infection occurs.

A particular variant of the HLA-DQA1 gene known as HLA-DQA1*02:01 increases the risk of liver damage in women with advanced breast cancer treated with a drug called lapatinib. Researchers suggest that the variant may increase immune system sensitivity to the drug, resulting in inflammation that damages the liver.