Hameed K, Bowman S, Kondeatis E, Vaughan R, Gibson T
Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan.
Br J Rheumatol. 1997 Nov;36(11):1184-8. doi: 10.1093/rheumatology/36.11.1184.
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.
特定的人类白细胞抗原-DR（HLA-DR）等位基因以及共同表位与类风湿关节炎（RA）之间的关联现已得到充分证实。这些关联的强度在不同种族之间有所差异。此外，在非欧洲人群中，共同表位的存在预示着严重疾病这一观点更难以成立。本研究首次调查了巴基斯坦人群中HLA-DR和HLA-DRB1的频率。采用聚合酶链反应（PCR）及序列特异性寡核苷酸探针（PCR-SSOP）和引物（PCR-SSP），确定了86例类风湿关节炎门诊患者及79例年龄、性别和种族相匹配的健康对照者的HLA-DR表型和基因型频率。患者和对照者中HLA-DR1和HLA-DR4的频率相似。HLA-DR10在类风湿关节炎患者中出现26例（15%），在对照者中出现8例（5%）（校正P值=0.048）。患者中HLA-DR2也有所增加（P=0.053），其主要亚型DR15显著增加（校正P值=0.03）。类风湿关节炎患者中HLA-DR5频率为5%，对照者中为19%（校正P值=0.002）。具有共同表位的HLA-DR4等位基因在类风湿关节炎患者中更为常见（校正P值=0.03），纳入其他具有共同表位的等位基因后，这种差异更加明显（校正P值=0.002）。43例（50%）患者和17例（22%）对照者中观察到共同表位等位基因（校正P值=0.003）。共同表位并不能区分病情更严重的患者，疼痛、关节畸形、残疾、类风湿因子或X线损伤均反映了这一点。类风湿关节炎巴基斯坦患者中HLA-DR等位基因的分布支持共同表位假说。与其他非欧洲种族群体一样，HLA-DR4与类风湿关节炎无关联。与其他群体不同的是，类风湿关节炎与HLA-DR2存在较弱的关联。HLA-DR5具有明显的保护作用。与其他一些研究一致，在这个门诊患者群体中，共同表位并非病情更严重的标志物。
