Intervertebral disc disease

Intervertebral disc disease is a common condition characterized by degeneration of one or more of the discs that separate the vertebrae, causing pain in the back or neck, and often in the legs and arms. The intervertebral discs provide cushioning between the vertebrae and absorb pressure on the spine. Although the discs of the lumbar region are the most affected in intervertebral disc disease, any part of the spine can have disc degeneration. Depending on the location of the affected disc or discs, this disease can cause periodic or chronic pain in the back or neck. The pain is often more severe when sitting, bending over, twisting, or lifting objects.

Degenerated discs are prone to herniation; the protruding disc may press against one of the spinal nerves that extend from the spinal cord to the rest of the body. This pressure causes pain, weakness, and numbness in the back and legs. Herniated discs often cause pain from the sciatic nerve, which runs from the lower back down each leg. Also, as a disc degenerates, bone spurs can form on the edges of the affected vertebrae. These bone spurs can compress spinal nerves, leading to weakness or numbness in the arms or legs. If the bone spurs compress the spinal cord, affected individuals may have trouble walking, as well as problems with bladder and bowel control. Over time, a degenerating disc can completely fragment, leaving no space between the vertebrae, which can lead to impaired movement, pain, and nerve damage.

This process is due to a combination of genetic and environmental factors. Some of these factors have been identified, but many remain unknown. Variations in several genes have been identified that may influence the risk of developing intervertebral disc disease. The genes most frequently involved in this process code for the synthesis of collagens that strengthen and support connective tissues, such as skin, bone, cartilage, tendons, and ligaments. Collagens form a network of fibers that create the structure and stability inside the intervertebral discs. Specific variations in several collagen-encoding genes appear to affect the risk of developing intervertebral disc disease by altering the ability of collagens to interact with one another, decreasing disc stability and causing disc degeneration.

Normal variations in genes related to the body´s immune function are also associated with an increased risk of developing intervertebral disc disease. These genes play a role in triggering an immune response when the body detects a foreign invader, such as a virus. It is believed that these genetic variants can provoke an immune response that leads to inflammation and dehydration of the discs, causing them to degenerate.

Similarly, variants in genes have been described that play a role in the development and maintenance of intervertebral discs and vertebrae associated with intervertebral disc disease. Associated variants can lead to disc degeneration and herniation. Work is ongoing to identify and confirm other genetic changes associated with an increased risk of the disease. In addition, non-genetic factors that contribute to disease risk are being studied, such as age, smoking, obesity, chronic inflammation, and driving for long periods of time.

Some of the identified genes associated with intervertebral disc disease include:

  • ACAN (aggrecan), 15q26.1.

  • ASPN (asporin), 9q22.31.

  • CILP (cartilage intermediate layer protein), 15q22.31.

  • COL1A1 (collagen type I alpha 1 chain), 17q21.33.

  • COL9A2  (collagen type IX alpha 2 chain), 1p34.2.

  • COL9A3 (collagen type IX alpha 3 chain), 20q13.33.

  • COL11A1 (collagen type XI alpha 1 chain), 1p21.1.

  • IGF1R (insulin like growth factor 1 receptor), 15q26.3.

  • IL1A (interleukin 1 alpha), 2q14.1.

  • MMP2 (matrix metallopeptidase 2), 16q12.2.

  • MMP9 (matrix metallopeptidase 9), 20q13.12.

  • THBS2 (thrombospondin 2), 6q27.

  • VDR (vitamin D (1,25- dihydroxyvitamin D3) receptor), 12q13.11.

Intervertebral disc disease can be hereditary, but the pattern of inheritance is generally unknown. People with a first-degree relative with intervertebral disc disease are at increased risk of developing the condition. People can inherit a genetic variation that increases the risk of intervertebral disc disease, but they do not inherit the disease itself. Not all people with intervertebral disc disease have a variation in one of the identified genes that increases risk, and not all people with a variation in these genes will develop the disease.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Intervertebral disc disease, by means of the complete PCR amplification of the exons of the ACAN, ASPN, CILP, COL1A1, COL9A2, COL9A3, COL11A1, IGF1R, IL1A, MMP2, MMP9, THBS2 and VDR genes, respectively, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes.