汉族类风湿关节炎患者HLA—DR和—DQ基因分型研究

为探讨ＨＬＡ－ＤＲ和－ＤＱ等位基因与我国汉族类风湿关节炎（ＲＡ）的相关性，采用聚合酶链反应－限制性内切酶片段长度多态性分析（ＰＣＲ－ＲＦＬＰ）方法对汉族人群中３５例ＲＡ患者和１００名健康人的ＤＲ和ＤＱ位点进行ＤＮＡ定型分析。结果发现，ＤＲ４频率在正常人为２４．０％，在ＲＡ患者为５１．４％（Ｐ＜０．０１，ＲＲ＝３．３０）；ＤＲ４亚型位点分析发现２组均以ＤＲＢ１＊０４０５占多数，但ＤＲＢ１＊０４０５频率在ＲＡ组为３１．４％，高于正常人的１０．０％（Ｐ＜０．０１）。ＤＱ４频率在全部ＲＡ患者为３７．１％，在ＤＲ＋４ＲＡ患者为７２．２％，均高于全部正常人的１０．０％（Ｐ＜０．０１）和ＤＲ＋４正常人的４１．６％（Ｐ＝０．０３７６）；ＤＲ＋４－ＤＱ＋４ＲＡ患者的病情重于ＤＲ－４患者。结果提示，ＤＲ４、主要是ＤＲＢ１＊０４０５与ＲＡ相关，ＤＱ４可增加ＤＲ４对ＲＡ的易感性，ＤＲ＋４－ＤＱ＋４单倍型是ＲＡ病情严重程度的标志。

DNA TYPING FOR HLA DR AND HLA DQ ALLELES IN CHINESE PATIENTS WITH RHEUMATOID ARTHRITIS

We analysed the associations of DR and DQ alleles with rheumatoid arthritis(RA) in Han nationality of China. PCR RFLP technique was used to determine DRB 1,DQA 1 and DQB 1 alleles in 35 unrelated patients with RA and 100 healthy controls from the Hans.The frequency of DR 4 was 51.4% in RA patients and 24.0% in the healthy controls ( P <0.01, RR =3.30).Subtyping of DR 4 revealed no differences in the relative distributions of the DR 4 alleles between the RA group and the controls,which both were predominated by DRB 1*0405 allele,but there was a significant increase in the absolute frequency of DRB 1*0405 in RA patients compared with the healthy controls (31.4% vs 12.0%, P <0.01). DQ 4 (DQB 1*04) was also increased both in the RA patients compared with the healthy controls ( 37.1% vs 10.0% , P <0.001) and in DR 4 RA patients compared with DR 4 healthy ones ( 72.2% vs 41.6% , P = 0.0376 ).Further analysis showed that the haplotype DR 4 DQ 4 was associated with RA ( RR = 5.17 , P < 0.001 ), and that the DR 4 DQ 4 patients had more severe disease than the DR - 4 patients. These results suggest that DR 4 , mainly the DRB 1*0405 ,is associated with RA in Han nationality,and DQ 4 may play a role in DR 4 conferring susceptibility to RA. The DR 4 DQ 4 haplotype could be taken as a predictive marker for disease severity.