ARE BOTH GENETIC AND REPRODUCTIVE ASSOCIATIONS WITH RHEUMATOID-ARTHRITIS LINKED TO PROLACTIN

The risk of rheumatoid arthritis (RA) seems to be associated with redu ced fecundity and with breastfeeding; these apparently contradictory r isk factors can be explained by their association with high prolactin concentrations. The only consistent genetic association with RA is for genes encoded in the HLA complex, particularly HLA DR4. We have ident ified some data indicating that the effects of breastfeeding and nulli parity are modified by HLA DR4 status, suggesting an interaction betwe en genetic and reproductive risk factors in the aetiology of RA. The p rolactin gene is in close proximity to the HLA region on the short arm of chromosome six. We therefore propose the hypothesis that the assoc iations between DR4 and reproductive risk factors in RA are due to lin kage disequilibrium between DR4 and an abnormally regulated prolactin gene polymorphism.