The association of HLA-DRB genes and the shared epitope with rheumatoid arthritis in Pakistan

Abstract

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.

Fcγ receptor type IIIA is associated with rheumatoid arthritis in two distinct ethnic groups

“…The shared epitope was present in 55% of UK Caucasian controls and in 17% of North Indian and Pakistani controls. The frequencies of the shared epitope in the UK Caucasian RA patient and control groups or the North Indian and Pakistani RA patient and control groups were comparable to those found in previously reported studies (18)(19)(20)(21). The association of the shared epitope with RA was similar for the UK Caucasian and North Indian and Pakistani cohorts (OR 3.3, 95% CI 1.8-5.9, P ϭ 0.000 and OR 4.2, 95% CI 2.2-7.8, P ϭ 0.000, respectively).…”

Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations

“…18 The Karachi South Asian population consisted of northern Indian, Punjabi, Memon and Ismaili. 19 We have also reassessed the initial three popu- 27.1 % = percentage of individuals positive; gf = gene frequency. *P c is calculated from 2 × 2 contingency of estimated chromosomes with that locus, corrected for the number of loci (n = 13).…”

“…Full details of sample collection are discussed elsewhere. 18 Seventy-eight healthy unrelated South Asian individuals from Karachi were also analysed; Hameed and coworkers 19 describe full details of ethnicity and sample collection. We also re-analysed three previous populations 14 using further PCR-SSP primer combinations which are described below.…”

Polymorphisme HLA et polyarthrite rhumatoïde précoce dans la population marocaine

“…Les autres allèles de susceptibilité connus (DRB1*01, DRB1*10 et DRB1*14) n'étaient pas associés avec la PR chez nos patients. La même observation a été rapportée par d'autres travaux réalisés chez des Arabes de différentes origines au Koweït [13], des Koweïtiens [18], des Pakistanais [27] et des Liguriens [28].…”