HLA-DR基因与类风湿关节炎关联性研究

Association between human leukocyte antigens-DR antigen genes and rheumatoid arthritis

目的：探讨人白细胞抗原（human leukocyte antigen，HLA）基因中的HLA-DR1-HLA-DR10等位基因与皖北地区汉族人群类风湿关节炎（RA）的临床表现、关节X线片影像及有关实验室检查结果的关联性。方法：选取RA患者80例与健康对照40名，采用特异性引物聚合酶链反应技术检测两组的HLA-DR1-HLA-DR10基因型，分析RA患者临床表现、X线片影像分期以及有关实验室检查结果与上述HLA-DR等位基因的关联性。结果：RA组HLA-DR4基因阳性率为35．0％，正常对照组为15．0％，两组差异有显著性（P〈0．05）。血清类风湿因子（RF）阳性和并发肺部病变的RA患者HLA-DR4阳性率均显著增高（P〈0．05和P〈0．005）。HLA-DR4阳性组与阴性组相比RF滴度较高，血沉较快，抗环瓜氨酸多肽（CCP）抗体水平较高（P〈0．05-P〈0．01）；HLA-DR4阳性组患者晨僵时间显著长于阴性组（P〈0．001）。关节功能为Ⅲ或Ⅳ级和X线分期为Ⅲ或Ⅳ期者亦以HLA-DR4阳性组显著为多（P〈0．01）。结论：皖北地区汉族人群RA易感性与HLA-DR4基因有关联性。HLA-DR4基因与晨僵时间、血沉、RF、抗CCP抗体、骨质侵蚀有一定联系，HLA-DR4阳性患者可能更容易发生肺部病变。

Objective：To investigate the association between the genes of human leukocyte antigens （HLA）-DR1 - DR10 and the clinical features,stages by X-ray image as well as the laboratory test results of rheumatoid arthritis（RA） in the population of Han nationality in northern Anhui province. Methods ：The method of amplification with polymerase chain reaction-sequence specific primer （PCR-SSP） was used to determine the HLA-DR1 - DR10 gene types in 80 patients with RA and 40 healthy controls from Han nationality in northern Anhui. The association between the gene types of HLA-DR and the clinical features ,X-ray stages of articulations and the laboratory test results were analyzed. Results ：The frequency of HLA-DR4 alleles was 35% in the RA patients and 15% in the healthy controls. The frequency of HLA-DR4 alleles was significantly higher in RA patients than that in normal subjects （ P 〈 0.05 ）. The frequency of HLA-DR4 alleles was higher in the group with positive sera of the rheumatoid factor（RF） and subsequent lung diseases（ P 〈 0.05 and P 〈 0.005 ）. The level of RF, anti-CCP antibody and erythrocyte sedimentation rate （ESR）in patients carrying HLA-DR4 gene was significantly higher than that of other patients（ P 〈 0.05 - P 〈 0.01 ）. The time of morning stiffness was longer in the patients with HLA-DR4 allele positive（ P 〈 0. 001 ）. The function and X-ray staging of articulations of class Ⅲ or Ⅳ were more frequently seen in patients with HLA-DR4 positive than in others（ P 〈 0.01 ）. Conclusions ：The susceptibility of RA is related to HLA- DR4 allele in the population of Han nationality in northern Anhui. HLA-DR4 allele may be related with the time of morning stiffness, level of RF and anti-CCP antibody,ESR and the degree of sclerotic erosion. Patients with HLA-DR4 positive arc more liable to acquire subsequent lung injury.