How do variations in the IL1A gene contribute to the development of inflammatory conditions like ankylosing spondylitis?

IL1A gene

The IL1A gene encodes a pro-inflammatory protein that plays a critical role in immune system communication and the body's defense against foreign invaders.

Normal Function

The IL1A gene provides instructions for making a protein called interleukin-1 alpha. Interleukins are a group of proteins made primarily in immune system cells that facilitate cell-to-cell communication. Interleukin-1 alpha is described as "pro-inflammatory" because it stimulates the activity of genes involved in inflammation and immunity, protecting the body from bacteria and viruses. It is also involved in bone resorption, the process of breaking down and removing bone tissue that is no longer needed.

Interleukin-1 alpha is initially produced as a precursor protein trapped within cells. A protein called calpain cleaves this precursor to create a shorter, mature version, which is then secreted by immune system cells to influence other cells.

Health Conditions Related to Genetic Changes

Ankylosing spondylitis

Several variations (polymorphisms) in the IL1A gene have been found to influence the risk of ankylosing spondylitis, a form of chronic inflammatory arthritis that primarily affects the spine. While it is not fully understood how these variations alter protein function, studies suggest the effects are likely related to the role of interleukin-1 alpha in promoting inflammation.

Other disorders

Variations in the IL1A gene have been studied as potential risk factors for several other disorders associated with abnormal inflammation, including:

Chronic gum (periodontal) disease
Chronic osteomyelitis (a progressive bone infection)
Open-angle glaucoma
Idiopathic inflammatory myopathy
Intervertebral disc disease
Keratoconus

The most well-studied variation is a change in a single DNA building block (nucleotide) in a regulatory region near the start of the gene (IL1A-889 C>T), which affects the production of interleukin-1 alpha. A second common variation (IL1A+4845 G>T) likely affects the sensitivity of the protein to cleavage by calpain.

Genomic Location

The IL1A gene is found on chromosome 2.