1. ¹University of Alabama at Birmingham, Birmingham, AL, USA
2. ²University of California, San Francisco, USA
3. ³University of California, Davis, USA

Correspondence: Dr SL Bridges Jr, Division of Clinical Immunology and Rheumatology, 412 Lyons-Harrison Research Building, University of Alabama at Birmingham, Birmingham, AL, 35294-0007, USA. E-mail: LBridges@uab.edu

Received 29 July 2004; Accepted 13 August 2004; Published online 4 November 2004.

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- (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.