Prognosis of the TNF Gene Polymorphism and Sarcoidosis

TNF基因多态性与结节病的预后

基本信息

批准号：
10670526
负责人：
YAMAGUCHI Etsuro
金额：
$ 1.92万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670526/
关键词：
tumor necrosis factor-β tumor necrosis factor-α sarcoidosis gene polymorphism TNF―β TNF―α

项目摘要

One hundred and ten Japanese patients with sarcoidosis and one hundred and sixty-one control subjects were genotyped for three biallelic polymorphisms in the promoter region of TNF-α gene and a Nco I polymorphism located in the first intron of the TNF-β gene. Frequencies of genotypes and alleles, and prognosis were assessed by logistic regression analysis or chi square analysis and the Cox proportional hazards model, respectively. There were no significant differences in the frequency of polymorphisms between patients and controls, thus indicating that none of the polymorphisms are markers for the susceptibility to sarcoidosis. However, the TNF-β gene polymorphism was associated with the clinical course of sarcoidosis in that patients with the allele TNFBィイD1*ィエD11 had a significantly more prolonged clinical course than those without the allele (probability for remission; 0.48). When the analysis was restricted to those without systemic corticosteroid therapy, the differences among the … More three genotypes (TNFBィイD1*ィエD11/1, TNFB*1/2, TNFB*2/2) were more overt (probability of remission; 0.33, 0.46, 1.00, respectively. When the analysis was restricted to those who could be followed for more than 60 months, similar results were found. In conclusion, the TNFB*1 allele was shown to be a marker for clinical course in patients with sarcoidosis.We next examined the cytokine production by blood lymphocytes stimulating them in vitro. The production of TNF-α in TNF-β genotypes TNFB*1/1, TNFB*1/2, TNFB*2/2 were 180 (mean)【minus-plus】100 (SD),206【minus-plus】126, and 268【minus-plus】223 pg/ml by stimulation with PHA, respectively, and 159【minus-plus】58、345【minus-plus】166、296【minus-plus】139 pg/ml by stimulation with anti-CD3 and anti-CD28 antibodies. The production of TNF-β were 520 (mean)【minus-plus】370 (SD), 325【minus-plus】145, and 298【minus-plus】100 pg/ml by stimulation with PHA, respectively, and 242【minus-plus】134, 481【minus-plus】320, 444【minus-plus】149 pg/ml by stimulation with anti-CD3 and anti-CD28 antibodies. There no significant differences in any of these cytokine levels, however, there was a tendency toward decreased production of TNF-α and TNF-β in subjects with the genotype TNFB*1/1 when lympcytes were stimulated with anti-CD3 and anti-CD28 antibodies. Less

在TNF-α基因的启动子区域和位于TNF-β基因的Firstron的TNF-α基因的启动子区域中，将一百十名日本患有结节病和161个对照受试者的患者进行基因分型基因型和等位基因的预后是通过逻辑回归或CHI平方分析评估的。 β基因多态性与患者S的临床过程相关，而TNFB I D1*II D11的临床延长延长了，而差异比没有等位基因的那些差异为0.48。 TNFB II D1*YIER D11/1，TNFB*1/2，TNFB*2/2）更为明显（缓解概率； 0.33、0.46、1.00，受访者。一个月，相似的结果。 TNFB*1的等位基因被证明是结节病患者的临床病程的标志。，TNFB*2/2为180（平均）[MINUS-PLUS] 100（SD），206 [MINUS-PLUS] 126和268 [MINUS-PLUS] 223 pg /ml，通过使用PHA刺激，恢复性，159 [[ Minus-Plus] 58，345 [Minus-Plus] 166，296 [Minus-Plus] 139 pg/ml，用抗CD3和抗CD28和抗CD28和抗体刺激。通过用PHA刺激145和298 [减去] 100 pg/ml，242 [MINUS-PLUS] 134，481 [MINUS-PLUS] S- Plus] 149 pg/ml，用抗CD28抗体刺激这些细胞因子水平中的任何一个均无显着的差异，当抗CD3和抗CD28抗体刺激lympcytes时，具有TNFB*1/1的受试者的TNF-α和β的产生趋势。