Evidence for a hypothetical non-HLA susceptibility gene in rheumatoid arthritis

In this study investigating possible reasons for the increased female prevalence of RA, family histories were obtained from 719 patients with classical RA by direct interview. Thirty-one per cent positively identified at least one affected relative. Compared with the expected population sex distribution ratio of 3:1 and local prevalence data, mothers with RA were eight times more common than predicted and fathers with RA 15 times more frequent. Mean age of onset of clinical disease was 7 yr younger in probands with affected fathers, compared to those with no or only maternal family history (P < 0.001). On the basis of other diseases where there is a gender discrepancy in prevalence, the characteristics of a major susceptibility gene product is proposed to connect these inheritance patterns with the known female preponderance for developing RA. Although there are clearly methodological uncertainties in a study of this type, it is felt that by concentrating on parental data only that these have been kept to a minimum, and that the conclusion is not unexpected.