Journal of Rheumatology. 2002;29, 11:2313-2318.
OBJECTIVE: To investigate the association of nodular disease in rheumatoid arthritis
(RA) with smoking, seropositivity, and polymorphisms at HLA-DRB1 and TNF loci. METHODS:
Consecutive patients with RA (n = 420) attending a hospital clinic were examined for
the presence of subcutaneous nodules. Rheumatoid factor (RF) status and HLA-DRB1 genotype
were determined on every patient, and their smoking history was recorded. TNFa microsatellite
polymorphisms were examined in a subgroup of 144 patients. The relationships between
smoking, RF status, HLA-DRB1 genotype, TNFa microsatellite polymorphism, and the presence
of nodules were examined using chi-square tests and logistic regression analyses.
RESULTS: Current smokers were more likely to have nodular disease than those who had
never smoked (OR 1.8, 95% CI 1.0-2.9). An association was also found between RF positivity
and nodular disease (OR 2.2, 95% CI 1.2-3.8) that remained significant after correction
for current smoking. A combination of current smoking and seropositivity increased
the risk of nodular disease (OR 3.9, 95% CI 1.7-9.1). Analysis of HLA-DRB1 genotypes
in this RA population revealed that only DRB1*0401 homozygotes were associated with
nodular disease, and that this was independent of the influence of smoking and seropositivity.
Individual TNFa microsatellite alleles were not associated with the presence of nodules,
but an interactive effect was found between the TNF a6 allele and homozygosity for
DRB1*0401. CONCLUSION: Our data indicate that nodular disease in RA is independently
associated with current cigarette smoking, seropositivity, and homozygosity for HLA-DRB1*0401.
The latter association involves a possible interaction with the TNF a6 microsatellite