HLA-DR基因与类风湿关节炎关联性研究

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。

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

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 are more liable to acquire subsequent lung injury.