Genetic risk factors for infection in patients with early rheumatoid arthritis.

Academic Article

Abstract

  • 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-alpha (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.
  • Published In

  • Genes and Immunity  Journal
  • Keywords

  • Age Factors, Aged, Arthritis, Rheumatoid, Etanercept, Female, Genetic Predisposition to Disease, Genotype, Humans, Immunoglobulin G, Lymphotoxin-alpha, Male, Methotrexate, Middle Aged, Polymorphism, Single Nucleotide, Prospective Studies, Receptors, IgG, Receptors, Tumor Necrosis Factor, Risk Factors, Tumor Necrosis Factor-alpha, Urinary Tract Infections
  • Digital Object Identifier (doi)

    Author List

  • Hughes LB; Criswell LA; Beasley TM; Edberg JC; Kimberly RP; Moreland LW; Seldin MF; Bridges SL
  • Start Page

  • 641
  • End Page

  • 647
  • Volume

  • 5
  • Issue

  • 8