Combination of Smoking and Absence of a Detoxifying EnzymeLinked to More Severe RA Disease in Female Patients

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Here's the text to which my previous post links (in case you don't want

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Combination of Smoking and Absence of a Detoxifying Enzyme Linked to

More Severe Rheumatoid Arthritis Disease in Female Patients

The Findings in a New Study Reveal a Surprising Conclusion

that Lung Cancer is not the only Consequence of Cigarette Smoking

In a recent study, researchers found an association between

cigarette smoking and a specific gene deletion that leads to more severe

Rheumatoid Arthritis (RA). According to the results of this study, which

is published in the March 2002 issue of Arthritis & Rheumatism, women

with RA who have smoked tobacco and lack the gene for a detoxifying

enzyme called the glutathione S-transferase M1 (GSTM1) are more likely

to have severe RA disease.

Rheumatoid Arthritis is a chronic, inflammatory, and

systemic disease that causes debilitating symptoms, including morning

stiffness, disfiguring painful joints, and skin nodules. An estimated

85% of RA patients have positive serum Rheumatoid Factor (RF), which is

often associated with more severe disease. While both genetic and

environmental factors are suspected to be contributory causes of RA, the

cause of RA is still unknown. Recent studies demonstrated that smoking

is linked to more severe RA disease and higher concentrations of RF. In

the A & R article, Dr. D.L. Mattey and colleagues demonstrated that

deletion of GSTM1 (a gene that codes for an enzyme that detoxifies

carcinogens found in tobacco smoke) that render it nonfunctional are

associated with more severe RA. Deleted GSTM1 is found in approximately

50% of Caucasians, and some studies have suggested that deletion GSTM1

gene is associated with smoking-related cancers and coronary artery

disease.

Postulating that smoking in patients lacking the GSTM1 gene

might play a role in development of severe RA, Mattey and colleagues

analyzed the association between GSTM1 genotype, smoking history, and

disease severity in a cross-sectional, retrospective study. 164 female

RA patients who fulfilled the American College of Rheumatology criteria

for RA and had the disease for at least 5 years were enrolled. Disease

severity was assessed using the Health Assessment Questionnaire (HAQ),

radiographic analysis using Larsen scores, and serum RF levels. Current

and past smoking history was quantified and categorized according to

" never smoked " and " ever smoked " ; " ever smokers " were further

subcategorized as past and current smokers. The GSTM1 genotype was

identified by extracting leukocyte DNA and using a polymerase chain

reaction assay to classify patients to GSTM1-1, the functional gene, and

GSTM1-null, the deleted gene.

Of the 164 women with RA, 51.3% were ever smokers, 29.9%

were current smokers and 58.5% had the GSTM1-null genotype. Past and

current smokers had significantly higher Larsen (a measure of x-ray

damage) and Health Assessment Questionnaire (HAQ) scores than

non-smokers, 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 GSTM1-1 patients with a smoking history.

GSTM1 status and smoking history were also strongly

associated with RF status and concentration. 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 status 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. " They

add, " our data also suggest that if smoking is involved in the

initiation process, it leads to more severe disease than it does in

patients in whom smoking is not involved (particularly if the patients

are GSTM1-null). "

Smoking and Disease Severity in Rheumatoid Arthritis:

Association with Polymorphism at the Glutathione S-Transferase M1 Locus,

L. Mattey, Hutchinson, T. Dawes, Nicola B. Nixon,

Sheila e, June Fisher, Ann Brownfield, Alldersea, A.

Fryer, and C. Strange, Arthritis & Rheumatism 2002, 46:3; pp.

640-646.