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 journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)641-647
Number of pages7
JournalGenes and Immunity
Volume5
Issue number8
DOIs
StatePublished - Dec 2004

Fingerprint

Rheumatoid Arthritis
Genotype
Alleles
Odds Ratio
Confidence Intervals
Infection
Urinary Tract Infections
Single Nucleotide Polymorphism
IgG Receptors
Lymphotoxin-alpha
Virus Diseases
Genetic Predisposition to Disease
Bacterial Infections
Methotrexate
Neutrophils
Clinical Trials
Genes

Keywords

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

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Hughes, L. B., Criswell, L. A., Beasley, T. M., Edberg, J. C., Kimberly, R. P., Moreland, L. W., ... Bridges, S. L. (2004). Genetic risk factors for infection in patients with early rheumatoid arthritis. Genes and Immunity, 5(8), 641-647. https://doi.org/10.1038/sj.gene.6364137

Genetic risk factors for infection in patients with early rheumatoid arthritis. / Hughes, L. B.; Criswell, L. A.; Beasley, T. M.; Edberg, J. C.; Kimberly, R. P.; Moreland, L. W.; Seldin, Michael F; Bridges, S. L.

In: Genes and Immunity, Vol. 5, No. 8, 12.2004, p. 641-647.

Research output: Contribution to journalArticle

Hughes, LB, Criswell, LA, Beasley, TM, Edberg, JC, Kimberly, RP, Moreland, LW, Seldin, MF & Bridges, SL 2004, 'Genetic risk factors for infection in patients with early rheumatoid arthritis', Genes and Immunity, vol. 5, no. 8, pp. 641-647. https://doi.org/10.1038/sj.gene.6364137
Hughes LB, Criswell LA, Beasley TM, Edberg JC, Kimberly RP, Moreland LW et al. Genetic risk factors for infection in patients with early rheumatoid arthritis. Genes and Immunity. 2004 Dec;5(8):641-647. https://doi.org/10.1038/sj.gene.6364137
Hughes, L. B. ; Criswell, L. A. ; Beasley, T. M. ; Edberg, J. C. ; Kimberly, R. P. ; Moreland, L. W. ; Seldin, Michael F ; Bridges, S. L. / Genetic risk factors for infection in patients with early rheumatoid arthritis. In: Genes and Immunity. 2004 ; Vol. 5, No. 8. pp. 641-647.
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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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