中国人群HLA－DR_4等位基因结构及其与类风湿关节炎相关性研究

对１３０名正常人及９５例类风湿关节炎（ＲＡ）病人ＨＬＡ－ＤＲ４基因分析结果显示，该基因与ＲＡ易感性显著相关（Ｐ＜０．００５），中国人群中至少存在８种ＤＲ４亚型，其中Ｄｗ１５（ＤＲＢ１０４０５）频率最高，占ＤＲ４阳性正常人的４８％，也是与ＲＡ易感性相关的主要亚型（ＲＲ＝３．１，Ｐ＜０．００５）。对ＤＲ４基因第二个外显子第三高变区分析结果显示，与ＲＡ易感性呈正相关的５种亚型均具有共同的Ｒ／ＫＲＡＡ序列特征，占病人ＤＲ４阳性群体的９２％，而正常人为５６％（Ｘ２＝１０．２９，Ｐ＜０．００５）。而３种与ＲＡ易感性呈负相关的ＤＲ４亚型均不具有上述序列特征。

The molecular basis of HLA DR4 alleles aweiatedwith rheumatoid arthritis in a Chinese population

LA-DR4 gene was studied by polymerase chainreaction method in 95 patients with rheumatoidarthritis(RA) and 130 nomial controls in a Shanghaipopulation. The results showed that the DR4 wassignificantly associated with RA(RR= 3. 1, X2 = 13.8,P < 0.005). The second exon of DR4 gene was also an-alysed by PCR-RFLP technique. There were at lesteight DR4 subtypes in this Chinese population. TheDRBI * 0405 (Dw15) was the most common allele.accounting for 48% of DR4 positive nonnal individ-uals and also is a principal subtype associated with RAsusceptibility (RR= 3.1, P<0.005). Analysis of thethird hyperpolymorphic region of DR4 positive sam-ples showed that 92% of patients had a sequenceencoding amino acids RRAA or KRAA comparedwith 56% of the DR4 positive controls (X2= 10.29,P < 0.005). All subtypes that were positively associatedwith RA susceptibility had the RRAA (DRB1 * 0404,0405, 0408 and 0410) or KRAA (DRBI * 0401) se-quences. while the negatively associated ones fDRBI0402, 0403 and 0406) had not. As a further evidence, itstrongly supported the " shared epitope" hypothesis.The different DR4 subtype structures and frequenciesmay account for the different associations of DR4with RA in various ethnic groups.