| Research Abstract |
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
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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
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