NEW YORK (Reuters Health) - Among women with rheumatoid arthritis, those who are smokers or ex-smokers and also lack a certain detoxifying enzyme are more likely than nonsmokers to develop severe disease, study results show.

The gene in question is GSTM1, which produces an enzyme that detoxifies cancer-causing chemicals in tobacco smoke. It is not uncommon for a person to be born without this gene.

"The prevalence of GSTM1 varies between different ethnic groups," Dr. Derek Mattey told Reuters Health. "For example, in Africans and African Americans, deletion of the GSTM1 gene is found in only 20% to 25% of individuals, compared to 50% to 55% of Caucasians. The frequency of this deletion in Asian populations is similar to that in Caucasians, although it may be slightly lower in Japanese."

Previous studies have shown that heavy smoking may influence the severity of rheumatoid arthritis. Unlike osteoarthritis, which is caused by the general wear and tear of aging, in rheumatoid arthritis the patient's immune system goes awry, attacking the joints and causing inflammation and stiffness. Mattey, a senior scientist at Staffordshire Rheumatology Centre in the UK, and his colleagues set out to discover what smoking has to do with this disease process.

They evaluated 164 northern European white women with rheumatoid arthritis. Eighty of the women had never smoked, 35 were ex-smokers and 49 were current smokers.

As in previous studies, rheumatoid arthritis was more severe in patients who were smokers or ex-smokers than in patients who had never smoked, Mattey's team reports in the March issue of Arthritis & Rheumatism. The team made the assessment using measures such as x-rays of joint damage and patients' ability to perform everyday tasks.

The researchers then divided the patients into those with or without the GSTM1 enzyme. In the group that lacked the enzyme, they found that rheumatoid arthritis severity was significantly greater in smokers and ex-smokers than in nonsmokers. In contrast, in the group that did have the GSTM1 enzyme, smoking did not influence disease severity.

The difference may be partly influenced by the body's production of a substance called rheumatoid factor, the research team suggests. Normally, the body produces molecules called antibodies to fight foreign organisms such as bacteria and viruses. One of the problems in rheumatoid arthritis is that the body produces antibodies against one of its own antibodies, IgG. These autoantibodies, as they are known, are also called rheumatoid factor.

"The majority of rheumatoid arthritis patients, 60% to 80%, are positive for rheumatoid factor," Mattey said. "The role of rheumatoid factor in the development of rheumatoid arthritis is still unclear, but it is generally considered to be a marker of more severe disease."

As in previous studies, the researchers determined that current smokers were significantly more likely to have rheumatoid factor than patients who had never smoked, and the number of years of smoking was associated with the amount of rheumatoid factor. A brand-new finding was that these facts held true only for patients who lacked the GSTM1 enzyme.

The explanation might be that chemicals in smoke damage IgG, prompting the body to produce more rheumatoid factor, the researchers propose. This would be much less of a problem in people who have the GSTM1 enzyme, which detoxifies these damaging chemicals.

Another finding from the study was that joint damage became just as severe in women who quit smoking once rheumatoid arthritis was diagnosed as in women who continued to smoke.

"This might suggest that cessation of smoking is of no value, in terms of preventing joint damage, once rheumatoid arthritis has developed," Mattey commented. "However, it may depend on how much they have smoked in the past, and previous light smokers may gain more benefit from stopping than previous heavy smokers.

"It needs to be borne in mind that this was a small study on a group of female patients in one particular geographic area. Smoking might be one of a number of possible factors that influence the severity of rheumatoid arthritis, such as diet, hormonal levels and exposure to environmental pollution," he pointed out.

"Also, it is very likely that other genes will be important in the association between smoking and severity of rheumatoid arthritis," he said. "Further studies are clearly needed to establish whether our findings apply to other populations of individuals with rheumatoid arthritis, and if other genetic factors are important."

SOURCE: Arthritis & Rheumatism 2002;46:640-646.

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