EVIDENCE FOR A HYPOTHETICAL NON-HLA SUSCEPTIBILITY GENE IN RHEUMATOID ARTHRITIS

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Abstract
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 sexdistribution 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.

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