Lack of association of the HLA-DRB1 shared epitope with RA

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Arthritis Rheum. 2004 Mar;50(3):753-62.

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.

Gorman JD, -Vaudey E, Pai M, Lum RF, Criswell LA.

University of California, San Francisco, and School of Public Health,

University of California, Berkeley.

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.

CONCLUSION: 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.

PMID: 15022316

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