INHERITANCE OF THE SHARED EPITOPE AND LONG-TERM OUTCOMES OF RHEUMATOID-ARTHRITIS AMONG COMMUNITY-BASED CAUCASIAN FEMALES

Multiple HLA-DRB1 alleles encoding a shared epitope (SE) at amino acid posi tions 70-74 are associated with susceptibility and severity of r heumatoid arthritis (RA). We examined the relationship between the num ber and DRB1 genotype of SE alleles inherited and long-term outcomes o f 180 community-based, Caucasian female RA patients followed annually for up to 12 years. Outcomes examined were physician assessment of RA course; annual measures of pain, function, and number of painful joint groups; history of joint surgery; and resource utilization. Models ac counted for correlation among serial observations for the same patient and adjusted for patient age and disease stage. We examined two genet ic models: a SE model in which patients were classified according to t he number of SE copies inherited and a genotype model in which patient s were categorized into one of six groups based on the inherited DRB1 genotype. We used likelihood ratio tests to compare these genetic mode ls and to compare alternative model specifications. Our results demons trate strong associations between inheritance of the SE and long-term outcomes of community-based Caucasian females with RA. However, the pa ttern of results is not consistent across the outcomes. An additive mo del of risk is apparent for history of joint surgery and RA hospitaliz ation. In contrast, a near reversal of this pattern is apparent for fu nction, joint pain, pain rating, and RA physician visits. Finally, alt hough the genotype model did not appear to be a better predictive mode l for RA outcomes overall, it did reveal some striking heterogeneity o f SE alleles that was masked by the more parsimonious SE model. For ex ample, the odds ratio (OR) for joint surgery for patients with 2 SE co pies (OR = 3.16) reflects an average of 2 very different ORs when pati ents are further categorized according to genotype groups 4 and 5 (OR = 1.3 and 11.9, respectively). (C) 1998 Wiley-Liss, Inc.