Back to Genetics: DNA variant may code for lumbar pain

It’s now tempting to blame your aching back on Mom and Dad. Researchers have discovered an inheritable gene variation that may increase susceptibility to lumbar-disk disease, a common precursor of lower-back pain.

The finding may lead to ways to identify patients at risk for lumbar-disk disease and to new drugs for treating it, says the study’s lead investigator, Shiro Ikegawa of the Institute of Physical and Chemical Research in Tokyo.

Lumbar-disk disease causes about a third of all back pain, which afflicts 70 to 90 percent of adults worldwide, says Tim Spector of St. Thomas’ Hospital in London. Lumbar disks, the pads of cartilage between vertebrae of the lower back, give the spine its flexibility and prevent vertebrae from rubbing together. In the disease, the disks’ spongy interior matrix dries out and the disks compress, pinching nerves or placing strain on the spine.

“As you compress the inside of the disk, you get instability and make it more susceptible to injury,” says Michael Shapiro of South Nassau Communities Hospital in Oceanside, N.Y. Eventually, the disk may rupture, necessitating surgery in some cases.

Ikegawa and his colleagues identified a genetic component in lumbar-disk disease by comparing the DNA of 188 people who have the disease and 367 people with healthy backs. People who have a variation in a gene that encodes the cartilage intermediate-layer protein (CILP), a normal component of disk tissue, were 1.6 times as likely to be in the disease group as in the healthy group. The gene variant yields a version of CILP that disrupts normal building and maintenance of cartilage, Ikegawa’s team reports in the June Nature Genetics.

Discovered in 1998, CILP had been implicated in osteoarthritis and some other degenerative cartilage diseases. To uncover CILP’s role in sore backs, Ikegawa and his group exposed rabbit disk-matrix cells to either normal CILP or the variant form.

In these tests, normal CILP slowed the activity of another protein, called TGF-b1, that normally regenerates cartilage matrix tissue, the team reports. However, the variant CILP inhibited TGF-b1 to an abnormal degree. Ikegawa proposes that the variant protein overzealously inhibits matrix-building activity.

If a drug were found to block the variant CILP’s influence, disk degeneration might be averted in individuals who carry the gene variant. “A search for drugs inhibiting the binding of CILP to TGF-b1 will be a key to develop this treatment,” says Junya Toguchida of Kyoto University in Japan.

Ikegawa’s report may spur more research on the role of genetics in cartilage problems and “should lead to other genes [involved in back pain] being unraveled in the same way,” Spector says.

Tim Flynn of Regis University in Denver, Colo., cautions that genetic factors won’t explain all lower-back problems. “Lifestyle, psychosocial issues, and other factors have been shown strongly to contribute to an individual’s lower-back health,” he says. So, even if your parents sometimes seemed like pains in the neck, they aren’t necessarily behind the pain in your back.

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