HLA-DQB1 gene

HLA-DQB1 gene

The HLA-DQB1 gene plays a critical role in the immune system by helping the body distinguish between its own proteins and those of foreign invaders.

Overview

The HLA-DQB1 gene provides instructions for making a protein that is part of the human leukocyte antigen (HLA) complex. This complex is the human version of the major histocompatibility complex (MHC), a gene family found in many species that helps the immune system identify and respond to threats like viruses and bacteria.

The HLA-DQB1 gene belongs to the MHC class II group. Proteins produced by these genes are found on the surface of certain immune system cells, where they attach to protein fragments (peptides) and display them to the immune system. If the immune system recognizes these peptides as foreign, it triggers an attack.

The protein produced from HLA-DQB1 binds to a protein from the HLA-DQA1 gene to form a functional complex called an antigen-binding DQαβ heterodimer. Because there are hundreds of variations (alleles) of this gene, the immune system can react to a wide range of invaders.

Health Conditions Related to Genetic Changes

Celiac disease

Specific combinations of HLA gene variants, known as haplotypes, increase the risk of celiac disease, an inflammatory disorder of the intestinal tract. These include:

• DQ2: Composed of HLA-DQB1 variants (HLA-DQB1*02:01 or HLA-DQB1*02:02) bound to HLA-DQA1 variants (HLA-DQA1*05:01 or HLA-DQA1*05:05).
• DQ8: Composed of the HLA-DQB1*03:02 variant bound to HLA-DQA1 variants (HLA-DQA1*03:01 or HLA-DQA1*03:02).

These haplotypes increase the risk of an inappropriate immune response to gluten. However, while these variants are found in 30 percent of the general population, only 3 percent of those individuals develop celiac disease.

Narcolepsy

The HLA-DQB1*06:02 variant increases the risk of narcolepsy, particularly in individuals with cataplexy (sudden loss of muscle tone). While the exact mechanism is unclear, evidence suggests narcolepsy may be related to an immune system malfunction that leads to the loss of hypocretin-producing neurons in the hypothalamus. Other genetic and environmental factors also contribute to the development of this disorder.

Type 1 diabetes

Type 1 diabetes risk is influenced by combinations of HLA-DQB1, HLA-DQA1, and HLA-DRB1. The highest risk is associated with two specific haplotypes:

• DR3:DRB1*03:01-DQA1*05:01-DQB1*02
• DR4:DRB1*04:01/02/04/05/08-DQA1*03:01-DQB1*02

Individuals with one copy of the DR3 haplotype and one copy of the DR4 haplotype in each cell are at the highest risk.

Other disorders

Normal variations of HLA-DQB1 have been associated with other autoimmune conditions, including:

• Multiple sclerosis: A chronic disorder of the central nervous system.
• Pemphigus: A condition causing severe blistering of the skin and mucous membranes.