Association of HLA-DRB1*02 with osteoarthritis in a cohort of 106 patients
Association of HLA-DRB1*02 with osteoarthritis in a cohort of 106 patients
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DOI：
10.1093/rheumatology/41.6.666
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发表时间：
2002-06-01
期刊：
影响因子：
5.5
通讯作者：
Müller, B
中科院分区：
文献类型：
--
作者：
Moos, V;Menard, J;Müller, B
Objective.我们先前已经表明，炎症细胞因子肿瘤坏死因子α（TNF-α）和白细胞介素（IL）6或IL-1 β在骨关节炎（OA）患者的软骨细胞中上调。然而，与OA相关的炎症反应是低级别和有限的。为了研究免疫系统在OA发病机制中的作用，我们分析了患者的HLA-DRB 1单倍型。结合单链寡核苷酸或序列特异性引物分型程序，随机选择139名对照和106名OA患者进行HLA-DRB 1等位基因分型。与对照组相比，OA组DR 2和DR 5等位基因的频率具有统计学显著性差异。虽然DR 2等位基因的频率在OA患者中升高，但DR 5等位基因与疾病呈负相关。DR 2和DR 5等位基因与对照组差异的P值分别为0.0431和0.0386，比值比分别为1.58和0.54。DR 2和DR 5与OA的关联提示HLA-DRB 1基因与OA发病相关基因之间存在连锁不平衡。或者，DR 2在限制对OA的低度炎症特征的免疫应答中具有直接作用。
Objective. We have previously shown that the inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin (IL) 6 or IL-1beta are up-regulated in chondrocytes of patients with osteoarthritis (OA). However, the inflammatory responses associated with OA are of low grade and restricted. To investigate the involvement of the immune system in the pathogenesis of OA, we analysed patients for their HLA-DRB1 haplotypes.Methods. Combining single-stranded oligo or sequence-specific primer typing procedures, 139 randomly selected controls and 106 OA patients were typed for their HLA-DRB1 alleles.Results. The OA cohort showed statistically significant differences in the frequencies of the DR2 and DR5 alleles compared with the controls. While the frequency of the DR2 allele was elevated among the OA patients, the DR5 allele was negatively associated with the disease. The P values for differences from the controls were 0.0431 for DR2 and 0.0386 for DR5 and the odds ratios for the two alleles were 1.58 and 0.54 respectively.Conclusion. The association of DR2 and DR5 with OA hints at linkage disequilibrium between HLA-DRB1 genes and genes involved in the pathogenesis of OA. Alternatively, DR2 has a direct role in restricting immunological responses to the low-grade inflammation characteristic of OA.