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Nodular Disease in Rheumatoid Arthritis: Association with Cigarette Smoking and HLA-DRB1/TNF Gene Interaction DEREK L. MATTEY, PETER T. DAWES, JUNE FISHER, ANN BROWNFIELD, WENDY THOMSON, ALI H. HAJEER, and WILLIAM E.R. OLLIER
ABSTRACT.
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 allele. (J Rheumatol 2002; 29:2313-8) Key Indexing Terms:
RHEUMATOID ARTHRITIS
From the Staffordshire Rheumatology Centre, Stoke-on-Trent, Staffordshire; and the ARC Epidemiology Unit, School of Epidemiology and Health Sciences, Manchester University Medical School, Manchester, UK. Supported by the Arthritis Research Campaign, the Haywood Rheumatism Research and Development Foundation, and the European Commission (contract BMH4-CT-0396). D.L. Mattey, PhD; P.T. Dawes, FRCP; J. Fisher, SRN; A. Brownfield, BSc, Staffordshire Rheumatology Centre; W. Thomson, PhD; A.H. Hajeer, PhD; W.E.R. Ollier, PhD, ARC Epidemiology Unit, School of Epidemiology and Health Sciences, Manchester University Medical School. Address reprint requests to Dr. D.L. Mattey, Staffordshire Rheumatology Centre, The Haywood, High Lane, Burslem, Stoke-on-Trent, Staffordshire, England ST6 7AG. E-mail: d.l.mattey@keele.ac.uk Submitted February 8, 2002; revision accepted May 22, 2002.
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