Extended reports
Association of oestrogen receptor gene polymorphisms with age at
onset of rheumatoid arthritis
Department of
Orthopaedic Surgery, Shiga University of Medical Science, Seta, Otsu,
520--2192, Japan
Correspondence to: Dr T Ushiyama.
Accepted for publication 8 October 1998
OBJECTIVE
In view of
the possible role of oestrogens in the pathogenesis of rheumatoid
arthritis (RA), this study investigated the association between
oestrogen receptor (OR) gene polymorphisms and RA.
METHODSPvu II and Xba
I restriction fragment length polymorphisms of the OR gene were
analysed in 70 male and 240 female patients with RA, and in 300 male
and 350 female controls. The absence or presence of restriction sites
were represented as P, p (Pvu II ) or X, x (Xba I ). The distribution
of OR genotypes was compared between the RA and control subjects by
sex. RA patients were divided into subgroups according to their OR
genotypes, then the age at onset, seropositivity, and rheumatoid nodule
positivity were compared between the subgroups.
RESULTSThe OR
genotype frequency of distribution did not have significant differences
between the male RA and male controls nor between the female RA and
female controls. In women with RA, there was a significant difference
of age at onset between the subgroups (uncorrected p=0.047, corrected
p=0.94). Female patients with the OR genotype PPxx (homozygote of
Px) tended to have developed RA at a younger age, whereas those with
PPXX and ppxx (lack of Px haplotype) developed RA at an older age. In
men with RA, there was no association between the OR genotype and age
at onset. In seropositivity and rheumatoid nodule positivity, there
was no significant difference between subgroups for either sex.
CONCLUSIONSSome
variants of the OR gene are related to the onset of RA in women in
certain age periods, suggesting the role of the interaction between the
OR gene and serum concentrations of oestrogen at the onset of the disease.
© 1999 by Annals of the Rheumatic Diseases
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