Genetic risk factors for infection in patients with early rheumatoid arthritis

L. B. Hughes, L. A. Criswell, T. M. Beasley, J. C. Edberg, R. P. Kimberly, L. W. Moreland, Michael F Seldin, S. L. Bridges

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


We analyzed clinical and genetic factors contributing to infections in 457 subjects with early rheumatoid arthritis (RA) enrolled in a prospective, 1-year clinical trial of methotrexate and the TNF inhibitor etanercept. Subjects were genotyped for the following single nucleotide polymorphisms (SNPs): (TNF -308, -238, and +488); lymphotoxin-α (LTA) (LTA +249, +365, and +720); and Fc gamma receptors FCGR2A 131 H/R, FCGR3A 176 F/V; and FCGR3B NA 1/2 and genotypes were correlated with infections. At least one URI was noted in 52% of subjects (99/191) with the NA2/NA2 genotype of the neutrophil-specific FCGR3B gene, compared to 42% (77/181) of those with the NA1/NA2 genotype and 39% (23/59) of those with the NA1/NA1 genotype (P=0.038). Urinary tract infection (UTI) was associated with the TNF -238 A (odds ratio(OR) 2.56, 95% confidence interval (CI) 1.05-6.25) and LTA +365 C (OR 1.73, 95% CI 1.07-2.79) alleles, and marginally with the FCGR3A F allele (OR 1.72, 95% CI 0.99-3.00). There was a striking linear correlation between UTI and the number of risk alleles defined by these three SNPs (P<0.001), suggesting an additive effect on susceptibility. These findings have important implications for the role of genetics in susceptibility to bacterial and viral infections.

Original languageEnglish (US)
Pages (from-to)641-647
Number of pages7
JournalGenes and Immunity
Issue number8
StatePublished - Dec 2004


  • Etanercept
  • Fc gamma receptor
  • Infection
  • Methotrexate
  • Rheumatoid arthritis
  • TNF

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics


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