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Genetic risk factors for infection in patients with early rheumatoid arthritis

Genes & Immunity volume 5, pages 641–647 (2004)Cite this 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-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.

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Acknowledgements

This work was supported by NIH R01 AR47224, P60 AR48095, the UAB Multidisciplinary Clinical Research Center Methodology Core; K24 AR-02175 and the Rosalind Russell Medical Research Center for Arthritis at UCSF. The technical assistance of Kevin N Turner, Blanche Woehl, Yuanqing Zhu, and Jinyi Wang is gratefully acknowledged.

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Authors and Affiliations

  1. University of Alabama at Birmingham, Birmingham, AL, USA

    L B Hughes, T M Beasley, J C Edberg, R P Kimberly, L W Moreland & S L Bridges Jr

  2. University of California, San Francisco, USA

    L A Criswell

  3. University of California, Davis, USA

    M F Seldin

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  1. L B Hughes
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Correspondence to S L Bridges Jr.

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Hughes, L., Criswell, L., Beasley, T. et al. Genetic risk factors for infection in patients with early rheumatoid arthritis. Genes Immun 5, 641–647 (2004). https://doi.org/10.1038/sj.gene.6364137

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