Objective: To test the hypothesis that the influence of the HLA-DRB1 shared epitope (SE) on the clinical manifestations of rheumatoid arthritis (RA) differs between men and women.
Methods: We assessed 777 consecutive RA patients for age at disease onset, articular manifestations, subcutaneous nodules, laboratory and radiographic findings, and treatment received. We typed HLA-DRB1 alleles by polymerase chain reaction-sequence-specific primer amplification and categorized the number of SE-containing alleles. We used regression models to adjust comparisons between the sexes for age and clustering by recruitment center, and included SE x sex interaction terms to look for heterogeneity between men and women in the effect of the SE.
Results: Among the 777 RA patients, 548 (71%) were women. Men and women differed significantly in the adjusted frequency of SE positivity (women 71.4% versus men 78.4%; P < or = 0.001). The SE was associated with a younger age at symptom onset and RA diagnosis among men, but not among women. The SE likewise had a significant adverse effect on joint tenderness, swelling, and deformity among men only. The SE was associated with a higher erythrocyte sedimentation rate in women and more frequent positivity for rheumatoid factor among both men and women.
Conclusion: There is heterogeneity between men and women in the effect of the SE on RA susceptibility and clinical expression. Further research is needed to understand the mechanism of this heterogeneity.