Prognosis of the TNF Gene Polymorphism and Sarcoidosis

TNF基因多态性与结节病的预后

• 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

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基因的第一个内含子中，对三个生物素质多态性的三个生物素多态性进行了基因分型，其中14例日本患有结节症和161个对照组的日本患者。基因型和等位基因的频率分别通过逻辑回归分析或CHI Square分析以及COX比例危害模型评估了预后。患者和对照组之间的多态性频率没有显着差异，因此表明多态性都不是对结节病的敏感性的标志。然而，TNF-β基因多态性与结节病的临床病程有关，因为患有TNFBIY D1*IY D11的患者的临床病程延长了比没有等位基因的患者的延长（0.48）。当分析仅限于没有全身性皮质类固醇治疗的分析时，……更多的三种基因型（TNFBII D1*IE D11/1，TNFB*1/2，TNFB*2/2）的差异更为明显（减排的可能性更高（缓解的可能性； 0.33，0.46，0.46，1.00，在分析中分析的时间比60个月相比。 TNFB*1的等位基因被证明是结节病患者的临床病程的标志。 206 [负率] 126和268 [Minus-Plus] 223 pg/ml，分别用PHA刺激和159 [Minus-Plus] 58，345 [Minus-Plus] 166，296 [Minus-Plus] 139 pg/ml通过用抗C-CD3和Anti-Cd28的刺激来刺激。 [MINUS-PLUS] 370（SD），325 [MINUS-PLUS] 145和298 [MINUS-PLUS] 100 pg/ml分别通过PHA刺激，和242 [Minus-Plus] 134，481 [Minus-Plus] [Minus-Plus] 320，444 [Minus-Plus] 149 Pg/ml tyan and tant and ant ant ant ant ant 2抗体。但是，这些细胞因子水平中的任何一个均无显着差异，但是，当用抗CD3和抗CD28抗体刺激淋巴细胞时，患有基因型TNFB*1/1受试者的受试者中TNF-α和TNF-β的产生趋势。较少的

项目成果

YamaguchiE, et al: "Tumor necrosis factor-β gene polymorphism is associated with the progasis of sarcoidosis" European Respintory Journal. 12(supp128). 332S (1998)

YamaguchiE 等人：“肿瘤坏死因子-β 基因多态性与结节病的进展相关”，《欧洲呼吸杂志》12（supp128）。

Yamaguchi E. et al.: "Genepolymorphism of tomornecros is foctors-α and βin sarcoiosis"Sarcoidosis Vasculitis and Diffuse Lung Disease. 16. s9 (1999)

Yamaguchi E. 等人：“结节病的基因多态性是结节病中的因子-α 和 β”，结节病血管炎和弥漫性肺病 16. s9 (1999)。

Yamaguchi E. et al.: "Tumor necros is factor(TNF) genepolymorphism is associated with prognosis of sarcoidosis"European Respie J. 12. s332 (1998)

Yamaguchi E.等人：“肿瘤坏死因子(TNF)基因多态性与结节病的预后相关”European Respie J. 12.s332(1998)

Yamaguchi, E.. et al.: "Gene polymorphisms of tumor necrosis factor-α and -β in sarcoidosis"Sarcoidosis Vasculitis and Diffuse Lung Disease. 16(Supl 1). 9 (1999)

Yamaguchi，E..等人：“结节病中肿瘤坏死因子-α和-β的基因多态性”结节病血管炎和弥漫性肺病16（增刊1）。