HFE GENE MUTATIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS.
J Li, Y. Zhu, DP Singal, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

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Since iron overload in synovial membranes has been observed in a number of patients with RA and since iron may play a role in sustaining inflammation, we examined the role of mutations in the HFE gene in susceptibility to RA. The distribution of C282Y and H63D mutations in 92 adult Caucasian patients with definite classical seropositive RA and 87 normal healthy Caucasian subjects was examined by the restriction endonuclease digestion of PCR-amplified genomic DNA. The prevalence of C282Y mutation in patients with RA was same as that in normal healthy controls. In contrast, the distribution of H63D mutation was significantly higher in total RA patient population (p<0.006, RR=2.54) and in RA susceptibility DRB1 QKRAA/QRRAA epitope-positive patients (p<0.005, RR=3.45) as compared to respective groups of normal subjects. Analysis of data showed that (i) both H63D mutation and QKRAA/QRRAA epitope are individually associated with RA, (ii) there is an interaction between these two factors in development of RA, and (iii) both these factors combined have stronger association with RA susceptibility than with these factors individually. H63D mutation therefore plays a role in pathogenesis or RA.