| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Genetic contribution of TAP1 and TAP2 genes to the pthogenesis of RA,PSS,SLE were studied using 92 RA patients, 55 PSS patients and 52 SLE patients. As a control, 95 normal Japanese sbjects were used. Associations of TAP genes with other genetic factors, such as HLA-DR et al, that was previously reported were studied and associations of TAP genes with clinical featres including autoantibodies were also examined. HLA-DR typing was carried out by PCR-RFLP method using several restrictin enzymes such as Sau3AI and AccI for TAP1, and BfaI,AccII,MspI and RsaI for TAP2. We used date of family history, age of onset, autoantibodies, et al.as clinical data. Significant associations between TAP1B and DR9, TAP2A and DR15, TAP2A and DRB1 ** 1502, TAP2B and DR8, and TAP2E and DR9 were shown. In RA not significant increses in prevalences of TAP2B and TAP2C were observed. TAP2E was significantly decreased. TAP2B and TAP2C showed positive association with HLA-DRB1**0405 in control. Association-analysi
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s between TAP and DR suggested that increasesin TAP2B and TAP2C were secondary to an increse in DRB1**0405. TAP2E showed no association with DRB1**0405 and it suggested the posibility that TAP2E had a protective role in pathogenesis of RA.An association of TAP2B and anti-SS-A Ab was also shown. In diffuse scleroderma (DS) and PSS with a-Scl-70 showed significant increased in TAP1A and TAP2A.A prevalence of TAP2B was significantly decreased in both PSS groups and TAP2B was decreased in DS.Association data between TAP and DR sggested that increases of TAP1A and TAP2A were secondary to an increases in DRB1**1502. No association was shown between TAP and clinical features including lung fibrosis. In SLE,no TAP alleles showed significant difference in prevalence and TAP2H showed a slight increas in SLE.Study of association between SLE related autoantiboty and TAP alleles showed a slight but not significant increase in TAP2H in RNP group. These result sggest that there was no association between TAP and autoantibody in SLE.Analysis using Odd ratio indicated that there was little possibility that TAP contribted additively to the pathogenesis of these autoimmune diseases in Japanese. We found a novel TAP2 gene allele (TAP2JT) that showed new RsaI RFLP pattern in one SLE patients. DNA sequence analysis showed a mutation of ATTATA*ATGAT at the position of 48723. We assigned it "TAP2JT". Less
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