title: Lack of association of the HLA-DRB1 shared epitope with rheumatoid nodules: an individual patient data meta-analysis of 3,272 Caucasian patients with rheumatoid arthritis.
abstract: OBJECTIVE
  The objective of this individual patient data (IPD) meta-analysis was to examine the relationship of rheumatoid nodules to the HLA-DRB1 shared epitope (SE) and to individual SE genotypes.
  
  
  METHODS
  English-language studies that enrolled adult non-Hispanic Caucasian patients with rheumatoid arthritis (RA) were identified by searches of Medline and Embase, and by manual searches of medical journals. All authors were contacted for IPD. Meta-analysis was performed to assess the association of SE presence, dose, and genotype with rheumatoid nodules. Meta-analyses adjusted for disease duration and cumulative meta-analyses were also performed to assess the influence of RA duration and year of study publication on the results.
  
  
  RESULTS
  A total of 24 studies and 3,272 patients were available for analysis. IPD were obtained for 22 of the studies. There was a nonsignificant association between the presence of the SE (i.e., 1 or 2 alleles versus 0 alleles) and rheumatoid nodules (summary odds ratio [OR] 1.3, 95% confidence interval [95% CI] 0.97-1.6). Analysis by SE genotype, however, demonstrated a weak relationship with inheritance of a single DRB1*0401 SE allele (OR 1.4, 95% CI 1.1-1.8). No other genotypes achieved statistical significance in the adjusted or unadjusted analyses.
  
  
  CONCLUSIONS
  The presence of the HLA-DRB1 SE does not appear to significantly increase the risk of rheumatoid nodules among Caucasian patients with RA. Analysis by DRB1 SE genotype was uninformative, suggesting only a potential (and at most modest) role of the DRB1*0401 SE allele. Results from this IPD meta-analysis implicate other genetic, stochastic, and/or environmental factors in the susceptibility to rheumatoid nodules.
authors.affiliation: University of California, San Francisco, and School of Public Health, University of California, Berkeley.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Gorman
authors.forename: Eve
authors.initials: E
authors.lastname: David-Vaudey
authors.forename: Madhukar
authors.initials: M
authors.lastname: Pai
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Lum
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
mesh_terms: D000368:Aged; D000939:Epitopes; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D012218:Rheumatoid Nodule / Q000235:genetics / Q000276:immunology*
chemical_list: D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen