Genetic risk factors for infection in patients with early rheumatoid arthritis.
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.
Hughes
L B
LB
University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA.
Criswell
L A
LA
Beasley
T M
TM
Edberg
J C
JC
Kimberly
R P
RP
Moreland
L W
LW
Seldin
M F
MF
Bridges
S L
SL
D000367:Age Factors; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D000068800:Etanercept; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017452:Receptors, IgG / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014552:Urinary Tract Infections / Q000150:complications / Q000235:genetics*
D007074:Immunoglobulin G; D008233:Lymphotoxin-alpha; D017452:Receptors, IgG; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept; D008727:Methotrexate