Differences between female and male patients with familial rheumatoid arthritis

Abstract

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.

Dissecting the heterogeneity of rheumatoid arthritis through linkage analysis of quantitative traits

“…Prior research has also provided evidence of an important role of male sex and environmental factors in RF autoantibody production (43)(44)(45). The differences in LOD score according to the sex of the sibpair members observed for certain chromosomes, such as the HLA region on chromosome 6p, are particularly striking and suggest interaction between sex and genes within these genomic regions.…”

Genetic Liability to Disability Pension in Women and Men: A Prospective Population-Based Twin Study

“…For example, sex-specific genetic factors have been reported to be influential on depression [8], [25], [26] and alcohol-related diagnoses [27]. Genetic heterogeneity between females and males was also demonstrated for rheumatoid arthritis [28]. In general, only a few studies include OS twin pairs and, therefore, the research on sex-specific genetic factors for different health outcomes is scarce.…”

Male Veterans Coping with the Pendulum Swing of Rheumatoid Arthritis Pain

“…The significance of studying RA in male veterans is that males have significantly higher risk (than females) for having specific shared epitope genotypes (HLA-DRB1), positive rheumatoid factor (RF), and anti-cyclic citrullinated polypeptide (anti-CCP) auto antibodies, all of which predispose men to poor outcomes, such as pain and disability and early mortality (Jawaheer, Lum, Gregersen & Criswell, 2006; Nagyova, Stewart, Macejova et al, 2005; Doran, Pond, Crowson et al, 2002; Mottonen, Paimela, Leirisalo-Repo et al, 1998). Although the causal role of gender-related hormones on diseases has not been fully explored (Wiesenfeld-Hallin; 2005), there is evidence to support that RA susceptibility (Laivoranta-Nyman, Luukkainen, Hakala et al, 2001) and disease course (Del Rincon, Battafarano, Arroyo et al, 2003) differ between males and females (Tengstrand, Ahlmen, Hafstrom et al, 2004), particularly in RA males who smoke (Jawaheer, Lum, Gregersen & Criswell, 2006). …”