Female Smokers Lacking Gene Risk Severe Arthritis

This finding is the result of a study by Dr. D.L. Mattey and colleagues of the North Staffordshire Hospital (Stoke-on-Trent, UK). Reported in the March 2002 issue of Arthritis & Rheumatism, the study showed that women with RA who smoke tobacco and lack the gene for the detoxifying enzyme glutathione S-transferase M1 (GSTM1) are more likely to have severe RA disease and higher levels of serum rheumatoid factor (RF) than are women nonsmokers.

Dr. Mattey and colleagues analyzed the association between GSTM1 genotype, smoking history, and disease severity in a cross-sectional retrospective study comprising 164 female RA patients who had the disease for at least five years. Disease severity was assessed using the Health Assessment Questionnaire (HAQ), radiographic analysis using Larsen scores (a measure of x-ray damage), and serum RF levels. Current and past smoking history was quantified and categorized according to never smoked, past smoker, and current smoker. The GSTM1 genotype was identified by extracting leukocyte DNA and using a polymerase chain reaction (PCR) assay to classify patients as being GSTM1-1 (possessing the functional gene) or GSTM1-null (lacking the gene).

Of the 164 women with RA, 51.3% were never smokers, 29.9% were current smokers and 58.5% had the GSTM1-null genotype. Past and current smokers had significantly higher Larsen and HAQ scores than nonsmokers, indicating more severe disease in RA patients with a smoking history. While the Larsen and HAQ scores did not significantly differ between GSTM1-1 and GSTM1-null patients after adjustment for age and disease duration, GSTM1-null patients with a history of smoking had significantly higher Larsen and HAQ scores than GSTM1-null patients who never smoked. Radiographic outcome was worse in GSTM1-null patients with a smoking history than in GSTM1-1 patients with a smoking history.

GSTM-1 status and smoking history were also strongly associated with RF levels. Among GSTM1-null patients, those with a smoking history were 3.1 times more likely to be RF positive than GSTM1-null patients who never smoked. GSTM1-null current smokers were 5.1 times more likely to be RF positive and more likely to have higher RF concentrations than GSTM1-null patients who never smoked. No significant difference in RF levels was found between GSTM1-1 patients with and without a smoking history.

The authors conclude that the data suggest, "that the risk of developing severe disease in female RA patients is increased in those who have the GSTM1-null polymorphism and who have also smoked.”