Researchers have found a link between combinations of certain rare gene mutations and fibromyalgia. The findings suggest a link to the body’s immune system and provide more evidence the disorder is inherited.
According to the National Fibromyalgia Association, the condition affects about 10 million people in the U.S., with women comprising 75 to 90 percent of those affected. In addition to pain, symptoms can include fatigue, sleep disorders, headaches, migraines and irritable bowel and bladder. Its cause remains unknown.
 John Shively (Photo by Darrin S. Joy) |
Researchers led at City of Hope by John Shively, Ph.D., chair of the Department of Immunology, and Steve Sommer, M.D., Ph.D., believe they have found a link between fibromyalgia and a gene involved with inflammatory response. They published their findings in the December 30, 2009, issue of PLoS ONE.
The gene, called MEFV, provides the coding for a protein found in certain white blood cells that play a role in inflammation. Scientists know that mutations in MEFV are associated with another disease called familial Mediterranean fever, which causes fever along with severe pain in the abdomen and joints and, in some cases, inflammation of the lung and heart linings. It sometimes can lead to kidney failure, arthritis and other disorders.
The research team chose to study MEFV because familial Mediterranean fever shares many symptoms with fibromyalgia.
Studying blood samples from 100 patients with fibromyalgia and their parents, the scientists scanned the MEFV gene for mutations. In 15 percent of the patients, they found 10 sets of rare genetic changes that were inherited from their parents at a frequency higher than expected.
“Since the mutations are rare, it is unlikely they would be transmitted from parent to child at a frequency greater than 50-50 unless they were associated with disease,” said Shively. “More likely, they are closely linked to the disease and therefore handed down from parent to child,” he said.
While other researchers have found evidence that fibromyalgia can be inherited, the current study provides a concrete link to specific mutations in a gene. The finding could one day open the door to genetic testing of fibromyalgia patients’ family members to help judge their risk of the disease, although the researchers caution more study is needed.
In addition to uncovering a possible genetic link, the research team also found further evidence suggesting that the immune system plays a part in fibromyalgia.
In previous studies, City of Hope researchers found increased levels of proteins linked to inflammatory response in fibromyalgia patients.
In the most recent study, the scientists found that families with any of the 10 sets of mutations in the MEFV gene had higher levels of a protein called interleukin-1 beta, or IL-1B, which is believed to cause some of the symptoms of familial Mediterranean fever.
“We didn’t see increased IL-1B levels in the 85 percent of fibromyalgia patients without the mutations,” said Shively, “so we are interested in sequencing other genes involved in inflammation in these patients to further test our hypothesis that fibromyalgia is associated with the immune system.”
Co-authors on the study included Jinong Feng, Ph.D., associate research scientist, and Zhifang Zhang, M.D., Ph.D., staff scientist; Shively credits the pair with performing most of the research. Co-authors R. Paul St. Amand, M.D., and Claudia Marek of the Fibromyalgia Treatment Center in Los Angeles, provided patient and family member blood samples.
The research was partially funded by a grant from the Los Angeles Fibromyalgia Foundation.
