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  • Title: Heterogeneity between men and women in the influence of the HLA-DRB1 shared epitope on the clinical expression of rheumatoid arthritis.
    Author: del Rincón I, Battafarano DF, Arroyo RA, Murphy FT, Escalante A.
    Journal: Arthritis Rheum; 2002 Jun; 46(6):1480-8. PubMed ID: 12115177.
    Abstract:
    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.
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