Arthritis and Rheumatism. 2002;46, 10:2716-2720.
OBJECTIVE: Although multiple associations between HLA loci and juvenile oligoarthritis
have previously been documented, evidence for linkage of HLA loci in oligoarthritis
in UK Caucasians with juvenile idiopathic arthritis (JIA) has not been described.
The aim of this study was to investigate linkage of HLA-A, B, and DRB1 in UK Caucasian
JIA patients with oligoarthritis. METHODS: One hundred forty-two families comprising
affected offspring and their parents (45 with one parent available and 97 with both
parents available) were typed for HLA-A, B, and DRB1 by polymerase chain reaction-sequence-specific
oligonucleotide probe. Single-point and multipoint analyses were performed using various
modifications of the extended transmission disequilibrium test. Linkage disequilibrium
(LD) analysis was performed using the EH-Plus system. RESULTS: Linkage to HLA-A and
HLA-DRB1 was seen in oligoarthritis and in the International League of Associations
for Rheumatology-defined subgroups of persistent oligoarthritis and extended oligoarthritis.
Linkage to HLA-A, B, and DRB1 was also observed in female patients with oligoarthritis.
Linkage of the HLA loci seemed to be attributable to maternal preferential transmission
of alleles. Furthermore, LD patterns between the HLA-A, B, and DRB1 loci were investigated.
HLA-A and HLA-DRB1 were confirmed as independent susceptibility loci for oligoarthritis.
CONCLUSION: This is the first study to establish linkage of HLA-A and HLA-DRB1 in
oligoarthritis and to show that the 2 loci contribute independently to disease. Further
studies are being performed to determine whether it is these loci or other genes in
LD with them that are responsible for susceptibility to oligoarthritis in UK Caucasian
patients with JIA