A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1 alpha polymorphism.
OBJECTIVE
The genetic factors that predispose to the development of juvenile rheumatoid arthritis (JRA) and its complications are not completely understood. The cytokine interleukin-1 (IL-1) has been implicated in the pathogenesis of JRA and other inflammatory diseases. This study was performed to test whether polymorphisms of the IL-1 alpha gene might be associated with JRA.


METHODS
We sequenced the 5' regulatory region (containing the promoter) of the human IL-1 alpha gene in 18 normal subjects. This revealed a C (IL-1A1) to T (IL-1A2) transition polymorphism at position -889. We studied the frequencies of both alleles in patients with JRA (n = 269) and controls (n = 99).


RESULTS
An increased gene carriage of IL-1A2 was found in patients with early-onset, pauciarticular JRA (EOPA-JRA; n = 103) compared with controls (0.66 versus 0.49; P = 0.01, odds ratio [OR] = 2.1). Within this subset of JRA, the association with IL-1A2 was particularly strong in the patients in whom chronic iridocyclitis developed (n = 28) compared with those without chronic iridocyclitis (0.89 versus 0.57; P = 0.002, OR = 6.2). Within the group of EOPA-JRA patients, IL-1A2 was also associated with elevation of the erythrocyte sedimentation rate (P < 0.0025).


CONCLUSIONS
This is the first report of a cytokine gene association with JRA, and we conclude that IL-1 alpha itself, or a gene for which the IL-1 alpha polymorphism is a marker, may contribute to the pathogenesis of EOPA-JRA and the ocular complications found in this group.
University of Sheffield, Royal Hallamshire Hospital, UK.
T L
TL
McDowell
J A
JA
Symons
R
R
Ploski
O
O
Førre
G W
GW
Duff
D000328:Adult; D000483:Alleles; D001171:Arthritis, Juvenile / Q000097:blood / Q000150:complications / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics; D001483:Base Sequence; D001799:Blood Sedimentation; D005787:Gene Frequency; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D015863:Iridocyclitis / Q000150:complications; D008969:Molecular Sequence Data; D009664:Norway; D011110:Polymorphism, Genetic
D007375:Interleukin-1