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 language | English (US) |
|---|---|
| Pages (from-to) | 641-647 |
| Number of pages | 7 |
| Journal | Genes and Immunity |
| Volume | 5 |
| Issue number | 8 |
| DOIs | |
| State | Published - Dec 2004 |
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Keywords
- Etanercept
- Fc gamma receptor
- Infection
- Methotrexate
- Rheumatoid arthritis
- TNF
ASJC Scopus subject areas
- Genetics(clinical)
- Immunology
- Genetics
Cite this
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 journal › Article
}
TY - JOUR
T1 - Genetic risk factors for infection in patients with early rheumatoid arthritis
AU - Hughes, L. B.
AU - Criswell, L. A.
AU - Beasley, T. M.
AU - Edberg, J. C.
AU - Kimberly, R. P.
AU - Moreland, L. W.
AU - Seldin, Michael F
AU - Bridges, S. L.
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
KW - Etanercept
KW - Fc gamma receptor
KW - Infection
KW - Methotrexate
KW - Rheumatoid arthritis
KW - TNF
UR - http://www.scopus.com/inward/record.url?scp=11044224426&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=11044224426&partnerID=8YFLogxK
U2 - 10.1038/sj.gene.6364137
DO - 10.1038/sj.gene.6364137
M3 - Article
C2 - 15526004
AN - SCOPUS:11044224426
VL - 5
SP - 641
EP - 647
JO - Genes and Immunity
JF - Genes and Immunity
SN - 1466-4879
IS - 8
ER -