Genetic cantribution of TAP1 and TAP2 genes to pathogenesis of RA,PSS and SLE

对92例RA、55例PSS和52例SLE患者进行了TAP 1和TAP 2基因在RA、PSS和SLE发病中的作用研究。以95例正常日本人作为对照。研究了TAP基因与其他遗传因素如HLA-DR等的相关性，并对TAP基因与自身抗体等临床特征的相关性进行了研究。应用限制性内切酶Sau 3AI和AccI对TAP 1进行分型，BfaI、AccII、MspI和RsaI对TAP 2进行分型。我们使用了家族史、发病年龄、自身抗体al.as临床资料。TAP 1B与DR 9、TAP 2A与DR 15、TAP 2A与DRB 1 ** 1502、TAP 2B与DR 8、TAP 2 E与DR 9之间存在显著相关性。在RA中，未观察到TAP 2B和TAP 2C的患病率显著增加。TAP 2 E显著降低。对照组TAP 2B、TAP 2C与HLA-DRB 1 **0405呈正相关。关联分析 ...更多信息 TAP与DR之间的相关性表明TAP 2B和TAP 2C的增加是DRB 1 **0405增加的继发因素。TAP 2 E与DRB 1 **0405无相关性，提示TAP 2 E在RA发病中可能具有保护作用，TAP 2B与抗SS-A抗体也有相关性。在弥漫性硬皮病（DS）和PSS中，a-Scl-70显示TAP 1A和TAP 2A显著增加。TAP 2B的患病率在两个PSS组中显著降低，并且TAP 2B在DS中降低。TAP和DR之间的关联数据表明，TAP 1A和TAP 2A的增加继发于DRB 1 **1502的增加。TAP与包括肺纤维化在内的临床特征之间无相关性。SLE患者TAP等位基因无显著性差异，TAP 2 H在SLE患者中略有增加，SLE相关自身抗体与TAP等位基因相关性研究显示，RNP患者TAP 2 H略有增加，但无显著性差异。这些结果表明，TAP与SLE自身抗体之间无相关性，用Odd比分析表明，在日本人中，TAP对这些自身免疫性疾病的发病机制几乎没有贡献。我们在一名系统性红斑狼疮患者中发现了一个新的TAP 2基因等位基因（TAP 2 JT），该基因表现出新的RsaI RFLP模式。DNA序列分析显示在48723位ATTATA*ATGAT突变。我们将其分配为“TAP 2 JT”。少

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 … More 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