汉族类风湿关节炎患者人白细胞抗原DR抗原β链多态性分析

Molecular analysis of HLA DRβ polymorphism in Han nationality patients with rheumatoid arthritis

目的探讨人白细胞抗原（ＨＬＡ）ＤＲ抗原中同源表位与我国汉族类风湿关节炎（ＲＡ）的相关性。方法采用聚合酶链限制片段长度多态性分析方法对汉族人群中１００名健康者和３５例ＲＡ患者的ＤＲ抗原β链进行了分析。结果ＤＲ４频率在正常对照组为２４．０％，在ＲＡ患者为５１．４％（Ｐ＜０．０１，ＲＲ＝３．３）。含有ＱＫＲＡＡ或ＱＲＲＡＡ同源表位的ＤＲ抗原阳性率在正常对照组为３０．０％，在ＲＡ组为６５．７％（Ｐ＜０．０１），在ＤＲ４＋正常对照组为７５．０％，及在ＤＲ４＋ＲＡ组为１００．０％（Ｐ＜０．０５）。在ＤＲ抗原的ＱＫＲＡＡ和Ｖ８５、Ｇ８６中有０～１个氨基酸被取代的个体中，ＲＡ占４８．８％，有２～３个氨基酸被取代者为１６．７％。结论ＤＲ４与我国汉族ＲＡ相关；ＤＲ抗原中ＱＫＲＡＡ或ＱＲＲＡＡ同源表位及Ｖ８５、Ｇ８６序列可能与ＲＡ的发病有关。

Objective To analyze the molecular basis for HLA-DR associations with rheumatoid arthritis(RA) in the han nationality of Chinese population. Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) techniques were used to dertermine DRB1 alleles in 35 unrelated patients with RA and 100 healthy controls from the Han nationality.Results The frequency of DR4(DRB1*04) was 51.4% in RA patients and 24 0% in the healthy controls( P <0 01, RR =3.3).There was a significant increase in the presence of the amino acid sequences QKRAA or QRRAA both in the RA patients overall compared with the healthy group(65.7% vs 30.0%, P <0 001) and in DR4 + RA patients compared with DR4 + healthy individuals(100% vs 75 0%, P <0.05) Substitution of residues in QKRAA, V85 and G86 appeared to correlate with relative risk for RA,among the subjects having 0～1 amino acid substitution,RA occurred in 48.8%,whereas in subjects with 2～3 amino acid changes,RA was present in only 16.7%.Conclusion These results suggest that DR4 is strongly associated with RA in the Han nationality, and the dominant effect that determines susceptibility to RA is associated with QKRAA or QRRAA as well as V85 and G86.