Rheumatoid Arthritis Riak Boosted by Gene Regulators

The kind of DNA once known as “junk” may influence people’s risk of getting rheumatoid arthritis, according to a study that offers the latest look at the complex system of switches that turn disease genes on.

Using genetic information from more than 300 people with rheumatoid arthritis and another 300 without, the researchers found 10 areas that appeared to influence risk, according to the research published yesterday in the journal Nature Biotechnology.

The finding builds on a growing body of evidence that genes, small pieces of DNA that make up about 1 percent of the genome, aren’t the only parts of the system that matter for disease risk. In September, a group of scientists created a map of the regulatory genes, and suggested they might be important for complex diseases like rheumatoid arthritis.

“This could explain why risk genes assert themselves and cause disease, and why some people are affected more easily than others,” said Tomas Ekstrom, a study author and professor of cell biology at the Karolinska Institutet, in a statement.

Rheumatoid arthritis, or RA, is a disease in which the immune system attacks the body, resulting in swelling and damage in the joints, which can make tasks such as walking or holding items painful. Women are more likely than men to have rheumatoid arthritis, and an estimated 1.5 million adults have the disease, according to the U.S. Centers for Disease Control and Prevention.

Changes in the junk DNA regulatory system may explain how the environment can influences inherited genes, the researchers wrote in the paper. One way that happens is in its ability to add or subtract pieces of DNA molecules. This process, called methylation, helps the body make sure that the correct genes are working at the right times.

Environmental Factors

“An example of this would be the gene variant that was previously linked to the increased risk of RA amongst smokers,” Ekstrom said. His group is now checking to see if there are regulatory regions that may explain the link between the inherited risk and the environment in rheumatoid arthritis.

In the study, researchers found changes in the regulatory system were associated with rheumatoid arthritis. Some of these influenced disease risk. Using mathematical modeling, the group found that some of these changes occurred only when people had particular gene variants. That suggests that the regulatory system is playing a role, the authors wrote.

Of the 10 areas discovered by the researchers, 9 were associated with a region known to play a role in diseases where the body attacks itself. One-tenth was on a region never-before associated with the disease. The findings were double-checked in a group of 12 people with rheumatoid arthritis and 12 controls.

Rheumatoid arthritis is treated with anti-inflammatory pills such as aspirin, or drugs such as Humira that attack the disease directly by modifying the immune system. Humira is made by AbbVie Inc., split off this month from Abbott Laboratories, and had $7.9 billion in 2011 sales, according to Abbott.

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