The research for the genetic factors of rheumatoid arthritis using the methods applying the polymorphism in microsatellites and the single nucleotide polymorphism

为阐明类风湿性关节炎(RA)的易感基因，本研究探讨了HL A-DR基因的作用及其遗传方式。利用受影响的同胞对对微卫星进行连锁分析，筛选出新的感病基因(区)。人类白细胞抗原共享表位(SE)分析显示，家族性RA与RNON家族性RA的共同表位(SE：69.8%和60.6%，DRI31*0405：45.3%和49.3%)中，SE尤其是HLA-DRB1*0405的参与程度基本相同。HLA-DRB1*0802不仅在随机RA和非家族性RA中显著降低，而且在家族性RA中也显著降低。HLA-DR以显性或加性遗传方式参与RA的发病。日本人MS等位基因频率与高加索人不同，约28.2%的MS杂合度小于0.7，约13.4%的MS杂合度小于0.6。使用53个家庭的初步数据显示，在9个地区，帐篷…的最大LOD值增加了1.2以上更确切地说是提拉1-9。Tiral-9位于Chr上105-141 cm处。3，25-50 GM on Chr.11，94.124个EM on Chr.17，0-33厘米。18，25.46厘米。X，8-41和140-155厘米。8，‘115-165 cm’，Chr.7，Chr.28-73 cm。2.候选区域(tiral-9)长288 cM，约占全基因组长度的8.3%。其他3个区域位于Chr上85-110 cm处。2，0-20 EM on Chr.Chr X上的139.165M cm具有较高的LOD评分(LOD&GT；0.8)，有可能成为敏感区。这些关于多发性硬化症的结果是这个阶段的初步结果，需要更多的检查才能完全证实结果。Cornrlis等在TIRA1和TIRA6中均表现为名义连锁，Jaw Aheer在TIRA1、TIRA3、TIRA5和TIRA6中均表现为名义连锁，Mackay在TIRA5中表现为名义连锁。许多可能的易感基因，如VIL2、TTTLEL、B4GALT4(在fiIRA1中)、0D44、BTF3、CD59(在TIRA2中)、ITGB4、AP4、TIMP2(在TIRA3中)、TGIF(在TIRA4中)、FIGF(在TIRA5中)、CTSB、PDGFRL(在TIRA6中)、SLAT4A(在TIRA7中)、Lamb1、PBEF、IRF5(在TIRA8中)以及TIMP3、ZNT3、LTBP1(在TIRA9中)都位于每个TIRA-区。经卡方检验，CTLA-4-3080等位基因与RA显著相关(P=0.048)，CTLA-4尚需进一步研究。较少

In this study the importance and the genetic mode of the contribution of HL A-DR was examined to clarify the susceptibility gene of rheumatoid arthritis (RA). The new susceptibility genes (areas) were also screened by the analysis of the linkage to micro-satellites using affected sib-pairs. HLA shared epitop a (SE) analysis showed the participation of SE, especially HLA-DRB1*0405 in familial RAwas almost as same as that in rnon-familial RA (SE : 69.8% and 60.6%, DRI31*0405: 45.3% and 49.3%, respectively). HLA-DRB1*0802 was signifioantly decreased not only in random and non-familial RA, but also in familial RA. HLA-DR contributed the pathogenesis of RA in the dominant or additive mode of inheritance. MS allele frequency in Japanese normal was different from Caucasian and about 28.2% of MS showed heterozygosity less than 0.7 and about 13.4% of MS, showed heterozygosity less than 0.6. Preliminary data using 53 families showed increases of maximum LOD score more than 1.2 in 9 regions, tent … More atively identified as TIRA 1-9. TIRAl-9 located at 105-141cM on Chr. 3, 25-50 GM on Chr. 11, 94.124 eM on Chr. 17, 0-33 cM on Chr. 18, 25.46 cM on Chr. X, 8-41 & 140-155 cM on Chr. 8,' 115-165 cM'on Chr. 7, and 28-73 cM on Chr. 2, respectively. Candidate regions (TIRAl-9) length 288 cM and is about 8.3 % of whole genome length. Other 3 regions located at 85-110 cM on Chr. 2, 0-20 eM on Chr. 3, and 139.165M cM on Chr X showed relatively high LOD score (LOD > 0.8) and have possibility as candidate of susceptibility area. These results in respect to MS are the preliminary results in this stage, and more examination is necessary to confirm the results completely. Cornrlis et all showed nominal linkage in TIRA1 and 6, and Jaw aheer showed nominal linkage in TIRA1, 3, 5 and 6. MacKay showed nominal linkage in TIRA5. Many plausible susceptibility genes, VIL2, TACTILE, B4GALT4 (in fiIRAl), 0D44, BTF3, CD59 (in TIRA2), ITGB4, AP4, TIMP2 (in TIRA3) TGIF (in TIRA4), FIGF (in TIRA5), CTSB, PDGFRL (in TIRA6), SLAT4A (in TIRA7), LAMB1, PBEF, IRF5 (in TIRA8), and TIMP3, ZNT3, LTBP1 (in TIRA9), locate in each TIRA-region. The CTLA-4 -3080 allele showed a significant association with RA by Ki-square test (p=0.048) and more examination is necessary on CTLA-4. Less