HLA-DRβ1*04亚型的氨基酸序列与类风湿关节炎易感相关性分析

The relationship between amino-acid motif of HLA-DRβ1*04(βchain) and the susceptibility to rheumatoid arthritis

目的研究HLA-DRβ1*01亚型的氨基酸序列与类风湿关节炎易感性的关系.方法选取类风湿关节炎患者136例,其他疾病对照组79例,以序列特异性引物PCR(PCR-SSP)技术对HLADRβ1 *04的36种基因亚型进行检测,并分析患者临床表现及血清学指标与各亚型氨基酸序列之间的关系.结果136例类风湿关节炎患者中46例出现HLA-DRβ1*04亚型阳性(33.8%),明显高于疾病对照组(12.7%)(OR=3.52,95%CI=1.43～5.43,P=0.001);RA患者的HLA-DRβ1*04亚型中的谷氨酰胺-赖氨酸或精氨酸-精氨酸-丙氨酸-丙氨酸(QK/RRAA)序列(22.1%)和谷氨酰胺-精氨酸-精氨酸-丙氨酸-谷氨酸(QRRAE)序列(9.6%)均分别高于疾病对照组(10.1%和1.3%)(OR=2.51、8.24,95%CI=1.05～4.52和1.01～56.64,P＜0.05);HLA-DRβ1*04亚型阳性组、QK/RRAA序列组及QRRAE序列组的关节畸形发生率、血清CRP和RF的阳性率均明显增高(P＜0.05);而含有QK/RRAA序列组与含有QRRAE序列组比较各项指标差异均无显著性(P＜0.05).结论HLA-DRβ1*04亚型是RA易感基因;携带QRRAE与QK/RRAA序列的RA患者关节受累明显,易发生关节畸形;HLA-DRβ1*04亚型中QRRAE序列与QK/RRAA序列均与RA的易感性有关.

Objective To investigate the susceptibility to rheumatoid arthritis (RA) with HLA- DRβ1*04 subtypes.Methods One hundred and thirty-six RA patients and 79 patients with other rheumatic diseases were recruited in this study.HLA typing was performed using high-resolution PCR-SSP DNA techniques.The clinical features and serologic markers between different motifs were analyzed.Results Compared with other rheumatic diseases,the frequency of HLA-DRβ1*04 alleles in RA patients was significantly increased(33.8% vs 12.7%)(OR=3.52,95%CI=1.43~5.43,P<0.001).The RA motifs QK/RRAA,QRRAE carried in HLA-DRβ1 alleles(22.1%;9.6%) were significantly higher in RA than other rheumatic diseases (10.1%; 1.3%)(OR=2.51;8.24,95%CI=1.05~4.52;1.01~56.64,P<0.05).HLA-DRβ1*04 alleles and QRRAE,QK/RRAA motifs in DRβ1 molecules were significantly related with severe RA.Incidences of RF and CRP were significantly higher in RA patients with HLA-DRβ1*04 alleles or QK/RRAA motifs (P<0.05).There were no significantl difference between patients with QK/RRAA and QRRAE motifs.Conclusions The results suggest that HLA-DRβ1*04 alleles are associated with RA.Both QRRAE and QK/RRAA motifs in HLA-DRβ1*04 are related to RA.The severity of RA is related to HLA-DRβ1*04 subtypes、QRRAE and QK/RRAA motif.QRRAE motif in HLA-DRβ1*04 may have the similar significance as QK/RRAA in RA.