The Genetics of Back Pain

By Delordson Kallon

Back Pain can be a debilitating condition which affects all aspects of a person's life and is responsible for a significant proportion of lost days from work. Governments and the health care sector spend a small fortune on both medication and physical therapy. Back Pain can be caused by physical trauma and general wear and tear but did you know that it can also have a genetic basis? A common example of Back Pain known to have a genetic association is Ankylosing Spondylitis (AS). Ankylosing Spondylitis is one of the major forms of chronic inflammatory arthritis. It is the prime example of a group of diseases known as Spondyloarthropathies. These are a group of chronic autoimmune joint diseases.

The key symptom of AS is arthritis affecting the spine and pelvis, more specifically, the sacroiliac joint. When it first starts, it presents with pain and reversible stiffness, that is, stiffness in the mornings that goes away later in the day with exercise. However in a proportion of cases, it gets progressively worse, leading to joint fusion, irreversible stiffness and deformity.

A large number of twin studies have been undertaken to try to understand the genetic basis of AS. These have confirmed that susceptibility to AS is determined by Human Leukocyte Antigen (HLA) genes. There is a strong association with the HLA class I gene HLA-B*27 (B27). This gene is found in more than of 90% of AS patients even though it is normally present in only 10% of the general population. The association between Ankylosing Spondylitis and HLA-B27 is amongst the strongest genetic associations with a common disease. It is surprising therefore that we still do not know for certain the actual mechanism by which the gene confers disease susceptibility.

The trigger for Ankylosing Spondylitis is thought to be exposure to a common environmental pathogen but beyond that, what is the actual molecular mechanism of the disease? A number of clever mechanisms have been proposed. These include the 'arthritogenic peptide' theory, the 'molecular mimicry' theory, endoplasmic reticulum stress due to B27 misfolding and accumulation and HLA-B27 homodimer expression. The 'arthritogenic peptide' theory says that Ankylosing Spondylitis develops from an HLA-B27 restricted T cell response to antigen found only in affected tissues such as the sacroiliac joint of the lower back. The molecular mimicry theory says that Ankylosing Spondylitis and its associated back pain develops from invading pathogens which share antigenic determinants with native cell surface antigens in the joint resulting in damage to the joints in the back.

Not all HLA-B*27 genes have an equal predisposing effect. HLA-B*27:02 and B*27:05 are known to be strongly associated but until recently, B*27:06 and B*27:09 were thought to be completely protective. However a small number of Ankylosing Spondylitis patients with chronic back pain who have these particular HLA alleles have now been reported in the scientific and medical literature. This means that B*27:06 and B*27:09 are protective only relative to the strongly associated alleles.

Testing and diagnosis of back pain primarily consists of physical examination, use of X rays or MRI and a check for family history however genetic testing for HLA-B*27 can be added to this diagnostic toolset. The strong association of HLA-B27 with Ankylosing Spondylitis makes B27 testing a useful component of the diagnostic work up. The value of genetic testing for back pain is that it allows a presumptive diagnosis to be made and early treatment in patients showing some of the symptoms. Waiting for a patient to fulfil all the classification criteria for a diagnosis of Ankylosing Spondylitis may been too late as significant damage to joints in the back would already have happened.