上海人群中TAP、LMP和HLA-DM基因多态性研究

Polymorphism of TAP,LMP and HLA-DM genes of Chinese Han population in Shanghai area

调查上海人群中抗原处理相关基因TAP、LMP和HLA-DM的分布情况,并探索这些基因与自身免疫病类风湿关节炎(RA)、IgA肾炎(IgAN)和多发性硬化症(MS)的可能关联。应用PCR-SSO或PCR-RFLP技术对80名无血缘关系的上海地区正常人及156名RA患者、60名IgAN患者和21名MS患者作了TAP1、TAP2、LMP2、HLA-DMA和HLA-DMB基因分型。并作了两位点连锁不平衡分析。在该群体中,(1)共观察到4个TAP1、6个TAP2、2个LMP2、4个HLA-DMA和4个HLA-DMB等位基因;(2)在TAP1B-TAP2A、TAP1B-LMP2H和TAP2D-DMA*0101存在连锁不平衡(Pc<0.05);(3)本人群中IgAN和MS的遗传易感性与抗原处理相关基因无关,而RA患者中DMB*0101基因频率降低(P<0.01),TAP1C和DMB*0104等位基因频率显著升高(P<0.01)。比较分析表明,上海人群中抗原处理相关基因多态性与国外其他人种中的报道相似,本人群中IgAN和MS与抗原处理相关基因不关联,而TAP1C和DMB*0104等位基因可能是RA的遗传易感基因。

In the present study, the distribution of genes associated with antigen processing （TAP, LMP and HLA-DM） of Chinese Han population in Shanghai area and the possible role of these genes in the genetie susceptibility to autoimmune diseaes, such as rheumatoid arthritis（RA）, IgA nephropathy（IgAN） and muhiple sclerosis（MS） were investigated, in which 80 normal healthy individuals, 156 patients with RA, 60 patients with IgAN and 21 pa tients with MS were randomly selected for study and genotyped for genes associated with antigen processing（TAP1, TAP2,LMP2, HLA-DMA and HLA-DMB） by using PCR-sequenee specific oligonucleolide（PCR-SSO） or PCR-rcstrietion fragment length polymorphism（PCR-RFLP） and two loci linkage disequilibrium analysis. In this population investigated, 4 TAP1, 6 TAP2, 2 LMP2, 4 DMA and 4 DMB alleles were observed. Linkage disequi-librium could be detected in TAP1B-TAP2A, TAP1B-LMP2H and TAP2D-DMA ＊ 0104 with statistically signifi cant differences. There was no correlation between the genctic susceptibility to IgAN and MS and genes associat-ed with antigen processing, but the gene frequency of DMB ＊ 0101 in patients with RA was significantly de-creased, but those of TAP1C and DMB ＊ 0104 were significantly increased. In conclusion, the polymorphisms of genes associated with antigen processing of Chinese Han population in Shanghai area are similar to those ob-served in other ethnic population, and no association is found between IgA nephropathy or muhiple sclerosis and the genes associated with antigen processing being tested. The TAP1C and DMB ＊ 0104 alleles may be the suseep-tibility gene for rheumatoid arthritis.