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Study Refutes Genetic Role in Rheumatoid Arthritis

Danish twin study suggests environmental factors are critical

FRIDAY, Feb. 1, 2002 (HealthDayNews) -- Genetics appears to take a backseat to environmental factors when it comes to raising the risk of rheumatoid arthritis.

A study by Danish scientists found that identical twins, who share the same genetic identity, were less likely than fraternal twins, who only share some genetic information, to have the disease, suggesting that genetics doesn't play a huge role in the risk of developing rheumatoid arthritis.

But another expert disagrees, saying that while environmental factors are important, genetic factors linked to the immune system play a major part in the development of the disease.

The findings appear in tomorrow's issue of the British Medical Journal.

Rheumatoid arthritis (RA) is a chronic disease in which the body's immune system mistakenly attacks the lining of joints and other internal organs. This can cause periods of pain, stiffness and swelling of the joints, which often become difficult to move.

The disease can also cause fever along with a loss of appetite and energy. People with rheumatoid arthritis (RA) experience characteristic periods of remission, followed by relapses.

The disease affects 2.1 million Americans, 1.5 million of them women. It generally strikes in middle age but can appear earlier. Some effective drug treatments are available, but there is no known cure.

The exact cause is unknown but studies have found that many people with RA have a genetic marker, known as the HLA complex, that affects the immune system.

The researchers used information from a Danish registry of identical and fraternal twins to contact 37,338 living twins about whether they had rheumatoid arthritis.

"It's important to use a population-based registry," says lead investigator Dr. Anders Svendsen. Previous studies had used patients recruited through arthritis clinics who also had a twin with arthritis, which tends to bias the sample of subjects towards female twins, identical twins, and twins who both have the disease.

In this study, those who responded positively were personally examined by Svendsen, who also examined medical records and verified the disease in 13 pairs of identical twins and 36 pairs of fraternal twins.

Although identical twins have the same genetic information, fraternal twins share about 50 percent of each other's genes. If identical twin sets had shared the disease more than fraternal twin sets did, the researchers could assume that it was due to their similar genetic setup.

But not a single pair of identical twins and only two pairs of fraternal twins both had rheumatoid arthritis, suggesting that the disease was no more common in twins whose genes were exactly the same.

"It was quite unexpected not to find any [identical] twins [who both had the disease]," says Svendsen.

"We know that there is a greater risk of being affected with rheumatoid arthritis if you have [certain immune markers such as HLA], but many people have them without developing rheumatoid arthritis," says Svendsen. Some patients have the disease without having the markers, "so they are neither necessary nor sufficient for the development of the disease."

Some research has suggested that an infectious agent, such as a virus, might cause the disease, but this has never been confirmed. Other risk factors, like diet, occupational exposures and smoking, have been examined, but researchers have not yet identified a specific environmental risk factor linked to the disease.

Dr. Peter Gregersen, the director of the Center for Genomics and Human Genetics at the North Shore-Long Island Jewish Research Institute in Manhasset, N.Y., praises the Danish study but notes that a larger sample of twin pairs would be helpful.

But he disagrees that genetics plays a minor role in rheumatoid arthritis. "There are several large genome-wide screens that unequivocally show that there is clearly something major going on in the HLA complex in terms of genes being linked to RA susceptibility," says Gregersen.

"There is clearly a non-genetic component that is substantial," says Gregersen, estimating that it accounts for about 50 percent of RA risk. He says that there's some evidence that smoking accounts for roughly a twofold increase in risk of the disease, while several studies have looked for a link between RA and the Epstein-Barr virus.

Svendsen's team is now working on a follow-up study of about 40,000 members of the Danish twin registry. They hope to confirm their findings and look at various environmental factors, including birth weight.

What To Do

For more information on rheumatoid arthritis, visit the Web sites for the Arthritis Foundation, the American College of Rheumatology, or the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

SOURCES: Interviews with Anders J. Svendsen, M.D., consultant, Department of Rheumatology, Odense University Hospital, Odense, Denmark; Peter K. Gregersen, M.D., director, Center for Genomics and Human Genetics, North Shore-Long Island Jewish Research Institute, Manhasset, N.Y.; Feb. 2, 2002, British Medical Journal
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