Polymorphism in the tumour necrosis factor receptor II gene is associated with circulating levels of soluble tumour necrosis factor receptors in rheumatoid arthritis.
Polymorphism in the tumour necrosis factor receptor II gene is associated with circulating levels of soluble tumour necrosis factor receptors in rheumatoid arthritis.
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DOI：
10.1186/ar1816
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发表时间：
2005
影响因子：
4.9
通讯作者：
Mattey DL
中科院分区：
文献类型：
--
作者：
Glossop JR;Dawes PT;Nixon NB;Mattey DL
可溶性肿瘤坏死因子受体（sTNFRs）水平在类风湿关节炎（RA）患者的循环中升高。尽管这些受体可以作为肿瘤坏死因子-α的天然抑制剂，但类风湿关节炎中sTNFRs的水平似乎不足以预防肿瘤坏死因子-α诱导的炎症。调控sTNFRs循环水平的因素尚不清楚，但肿瘤坏死因子受体基因的多态性可能起作用。我们研究了两组高加索类风湿性关节炎患者肿瘤坏死因子受体I （TNF-RI）和II （TNF-RII）基因多态性与sTNFRs水平之间的关系：一组为早期（病程≤2年，n = 103），一组为确诊（病程≥5年，n = 151）。采用PCR限制性片段长度多态性分析对患者进行TNF-RI基因的A36G多态性和TNF-RII基因的T676G多态性的基因分型。采用ELISA法检测sTNFRs水平。我们还从58例已知TNF-R基因型的RA患者的外周血中分离出T细胞，并在有或不含植物血凝素的细胞中检测sTNFRs向培养基中的释放。两种sTNFR （sTNF-RI和sTNF-RII）的血清水平在两组人群中均呈正相关，且两种sTNFR水平在已确诊疾病患者中均显著升高（P < 0.0001）。校正了年龄、性别和病程的多元回归分析显示，在已确诊疾病的患者中，不同TNF-RII基因型（TT > TG > GG）的sTNF-RI和sTNF-RII水平均有显著下降趋势（P为趋势= 0.01，P为趋势= 0.03）。在早期疾病中也有类似的不显著趋势。与TNF-RI A36G多态性无关系。分离的T细胞释放的sTNFRs根据TNF-RII基因型表现出类似的水平下降趋势，尽管仅与sTNF-RII水平相关。体外循环sTNFRs水平与T细胞释放水平之间存在很强的相关性。我们的数据表明，TNF-RII中的T676G多态性与外周血T细胞释放的sTNFR水平以及RA患者循环中的sTNFR水平相关。
Levels of soluble tumour necrosis factor receptors (sTNFRs) are elevated in the circulation of patients with rheumatoid arthritis (RA). Although these receptors can act as natural inhibitors of tumour necrosis factor-α, levels of sTNFRs in RA appear to be insufficient to prevent tumour necrosis factor-α induced inflammation. The factors that regulate circulating levels of sTNFRs are unclear, but polymorphisms in the tumour necrosis factor receptor genes may play a role. We investigated the relationship between polymorphisms in the tumour necrosis factor receptor I (TNF-RI) and II (TNF-RII) genes and levels of sTNFRs in two groups of Caucasian RA patients: one with early (disease duration ≤2 years; n = 103) and one with established disease (disease duration ≥5 years; n = 151). PCR restriction fragment length polymorphism analysis was used to genotype patients for the A36G polymorphism in the TNF-RI gene and the T676G polymorphism in TNF-RII. Levels of sTNFRs were measured using ELISA. We also isolated T cells from peripheral blood of 58 patients with established RA with known TNF-R genotypes, and release of sTNFRs into the culture medium was measured in cells incubated with or without phytohaemagglutinin. Serum levels of the two sTNFRs (sTNF-RI and sTNF-RII) were positively correlated in both populations, and the level of each sTNFR was significantly higher in the patients with established disease (P < 0.0001). Multiple regression analyses corrected for age, sex and disease duration revealed a significant trend toward decreasing sTNF-RI and sTNF-RII levels across the TNF-RII genotypes (TT > TG > GG) of patients with established disease (P for trend = 0.01 and P for trend = 0.03, respectively). A similar nonsignificant trend was seen for early disease. No relationship with the TNF-RI A36G polymorphism was observed. sTNFRs released by isolated T cells exhibited a similar trend toward decreasing levels according to TNF-RII genotype, although only the association with levels of sTNF-RII was significant. Strong correlations were found between levels of circulating sTNFRs and levels released by T cells in vitro. Our data indicate that the T676G polymorphism in TNF-RII is associated with levels of sTNFRs released from peripheral blood T cells, and with circulating levels of sTNFR in patients with RA.
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影响因子：
--
作者：
Bridges, SL;Jenq, G;McNicholl, J
通讯作者：
McNicholl, J
影响因子：
5.4
作者：
BRENNAN, FM;GIBBONS, DL;FELDMANN, M
通讯作者：
FELDMANN, M
DOI：
10.1159/000133127
发表时间：
1991-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
BAKER, E;CHEN, LZ;SUTHERLAND, GR
通讯作者：
SUTHERLAND, GR
影响因子：
3.8
作者：
DEMBIC Z;LOETSCHER H;LESSLAUER W
通讯作者：
LESSLAUER W
影响因子：
--
作者：
DELEURAN, BW;CHU, CQ;MAINI, RN
通讯作者：
MAINI, RN