title: Genetic risk factors for infection in patients with early rheumatoid arthritis.
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-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.
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Hughes
authors.forename: L A
authors.initials: LA
authors.lastname: Criswell
authors.forename: T M
authors.initials: TM
authors.lastname: Beasley
authors.forename: J C
authors.initials: JC
authors.lastname: Edberg
authors.forename: R P
authors.initials: RP
authors.lastname: Kimberly
authors.forename: L W
authors.initials: LW
authors.lastname: Moreland
authors.forename: M F
authors.initials: MF
authors.lastname: Seldin
authors.forename: S L
authors.initials: SL
authors.lastname: Bridges
mesh_terms: 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*
chemical_list: D007074:Immunoglobulin G; D008233:Lymphotoxin-alpha; D017452:Receptors, IgG; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept; D008727:Methotrexate