The British Journal of Rheumatology, Vol 36, 1184-1188, Copyright © 1997 by British Society for Rheumatology
K Hameed, S Bowman, E Kondeatis, R Vaughan and T Gibson
The association of particular HLA-DR alleles and the shared epitope with
rheumatoid arthritis (RA) is now well established. The strength of these
links varies between races. Furthermore, the proposition that the presence
of the shared epitope is indicative of severe disease has been more
difficult to sustain in non-Europeans. This study examines the frequency of
HLA-DR and HLA-DRB1 amongst Pakistanis for the first time. Using the
polymerase chain reaction (PCR) and sequence-specific oligonucleotide
probes (PCR-SSOP) and primers (PCR-SSP), HLA-DR phenotype and genotype
frequencies were ascertained in 86 RA hospital out-patients and 79 healthy
controls matched for age, gender and ethnicity. HLA-DR1 and HLA-DR4
frequency was similar in patients and controls. HLA-DR10 occurred in 26
instances (15%) in RA and in eight (5%) controls (Pcorr = 0.048). HLA-DR2
was also increased in patients (P = 0.053) and its major subtype DR15 was
significantly increased (Pcorr = 0.03). HLA-DR5 frequency was 5% in
patients and 19% in controls (Pcorr = 0.002). The HLA-DR4 alleles
possessing the shared epitope were more common in RA (Pcorr = 0.03) and
this difference was enhanced by inclusion of other alleles possessing the
shared epitope (Pcorr = 0.002). Shared epitope alleles were observed in 43
(50%) patients and 17 (22%) controls (Pcorr = 0.003). The shared epitope
did not distinguish patients with more severe disease, as reflected by
pain, joint deformities, disability, rheumatoid factor or X-ray damage. The
distribution of HLA-DR alleles in Pakistanis with RA supports the shared
epitope hypothesis. In common with other non-European racial groups,
HLA-DR4 was not associated with RA. Unlike other groups, there was a weak
link of RA with HLA-DR2. A protective effect of HLA-DR5 was apparent. In
accord with some other studies, the shared epitope in this hospital
out-patient population was not a marker for more severe disease.
ORIGINAL PAPERS
The association of HLA-DRB genes and the shared epitope with rheumatoid arthritis in Pakistan
Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan.
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