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Are both genetic and reproductive associations with
rheumatoid arthritis linked to prolactin?

Brennan P, Ollier B, Worthington J, Hajeer A, Silman A

Arthritis and Rheumatism Council Epidemiological Research Unit,
University of Manchester Medical
School, UK.

The risk of rheumatoid arthritis (RA) seems to be associated with
reduced fecundity and with
breastfeeding; these apparently contradictory risk 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 identified some data
indicating that the effects of
breastfeeding and nulliparity are modified by HLA DR4 status, suggesting
an interaction between genetic
and reproductive risk factors in the aetiology of RA. The prolactin gene
is in close proximity to the HLA
region on the short arm of chromosome six. We therefore propose the
hypothesis that the associations
between DR4 and reproductive risk factors in RA are due to linkage
disequilibrium between DR4 and an
abnormally regulated prolactin gene polymorphism.

MeSH Terms:

    Arthritis, Rheumatoid/genetics*
    Arthritis, Rheumatoid/etiology