Objective-To determine whether there are genetic diVerences between female and male patients with familial rheumatoid arthritis (RA). Methods-45 men and 119 women from 78 families with RA who all had at least one first degree relative with RA were compared. HLA-DRB1 alleles were analysed, including DRB1*04 subtypes and associations of DRB1*04 haplotypes with DQB1*0301 or DQB1*0302 alleles, the age of the patients at disease onset, the presence of rheumatoid factor (RF), joint erosions, and rheumatoid nodules. Results-HLA-DRB1*13 allele (the subtype allele of DR6, reported to be protective against the development of RA) was found in 14/119 (12%) of female but in none of the male patients (p=0.036). The HLA-DR4 allele was found slightly more often in men than women patients with familial RA (31/45 (69%) v 75/119 (63%), NS). Men were also more often RF positive than women (44/45 (98%) v 98/117 (84%); p=0.031). On the other hand, the mean age at onset of RA was significantly lower in the female group (40.4 years) than in men (46.6 years, p=0.0044). Conclusion-The results indicate that there is stronger genetic background in familial male than female patients with RA in the genetic susceptibility defined by the studied HLA antigens. However, the earlier age of onset of the disease in female group and the increased proportion of women with RA indicate that there are additional sex related predisposing factors enhanced in familial cases. (Ann Rheum Dis 2001;60:413-415) The ratio of the prevalence of women to men with rheumatoid arthritis (RA) has been consistently found to be around 3:1, 1 though the probands from multicase families have been reported as often to be men as women. 2The observations that more women than men develop RA implies the presence of major susceptibility factor(s) other than HLA in female patients.3 These might be hormonal or sex related genetic factors. 4 Some studies suggest that the strength of the known HLA-DR4 association of RA is weaker in women than in men, 4-6 but this has not been confirmed in other studies.3 7 A higher proportion of HLA-DR4 antigen in men than in women might be related to the presence of other susceptibility factors in women.

Objective-To search for possible immunogenetic diVerencies between the patients with familial and non-familial rheumatoid arthritis (RA). Methods-The study compared 129 familial RA patients with 217 non-familial patients for the frequencies of HLA-DR antigens including DR4 subtypes, DR4-DQB1*0301 and DR4-DQB1*0302 haplotypes and HLA-B27 antigen as well as the age of disease onset and existence of rheumatoid factor or joint erosions. Results-Two major diVerences between familial and non-familial groups were found: firstly, familial RA patients had increased frequency of HLA-DR4 as compared with the non-familial RA group (68.2 v 54.8%; p = 0.019). Secondly, the mean age at onset of RA was significantly lower in the familial than in the sporadic RA patients (42.0 v 46.5 years; p = 0.0020) and the diVerence still remained when the DR4 positive and negative subgroups were compared separately. Conclusion-These results confirm the more prominent association with HLA-DR4 in familial than in the non-familial cases and suggest that accumulation of HLA risk genes may, at least partly, explain the familial occurrence of the disease. Other susceptibility genes may also be concentrated in multiplex case families as suggested by an earlier age at the onset of RA in both HLA-DR4 positive and negative familial patients.