Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in pre-eclampsia
Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in pre-eclampsia
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DOI：
10.1046/j.1365-2249.1996.d01-647.x
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发表时间：
1996-04-01
影响因子：
4.6
通讯作者：
McKillop, JH
中科院分区：
文献类型：
--
作者：
Chen, G;Wilson, R;McKillop, JH
子痫前期是一种内皮功能紊乱，肿瘤坏死因子-α通过多种途径对内皮细胞产生基础性作用，包括改变氧化剂和抗氧化剂之间的平衡，改变前列腺素的产生模式，影响几种细胞表面成分的表达。为探讨子痫前期患者外周血中肿瘤坏死因子-α(TNF-α)的表达水平，采用定量逆转录-聚合酶链式反应(RT-PCR)方法检测了子痫前期患者、正常妊娠妇女和正常非妊娠妇女的外周血白细胞中肿瘤坏死因子-α的表达。采用373AABI测序仪模型，应用GENESCAN和Genotyper软件对肿瘤坏死因子-α基因多态性进行分析，以解释肿瘤坏死因子-α基因异常表达的机制。我们的结果显示，与其他两个对照组相比，子痫前期患者血清中肿瘤坏死因子-α的表达水平显著升高。肿瘤坏死因子-α的高表达可能与TNF1等位基因有关，该等位基因在子痫前期患者中的频率明显升高。这些观察结果与肿瘤坏死因子-α在调节内皮功能紊乱中的主要作用是一致的，并提示肿瘤坏死因子-α在先兆子痫的发生发展中起着关键作用。
Pre-eclampsia is an endothelial disorder and TNF-alpha has fundamental effects on endothelial cells by several means, including altering the balance between oxidant and anti-oxidant, changing the pattern of prostaglandin production and affecting expression of several cell surface components. To determine whether TNF-alpha mRNA expression is increased in pre-eclamptic patients, leucocytes from pre-eclamptic patients, normal pregnant women and normal non-pregnant women were studied for TNF-alpha expression using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Using a model of 373A ABI Sequencer, TNF-alpha gene polymorphism was also analysed by GENESCAN and Genotyper software in order to explain the mechanism of abnormal TNF-alpha expression. Our results show that TNF-alpha mRNA expression is significantly elevated in preeclamptic patients compared with the other two control groups. The high expression of TNF-alpha may be associated with the TNF1 allele, whose frequency is markedly increased in pre-eclamptic patients. These observations are consistent with a major role for TNF-alpha in mediating endothelial disturbances, and suggest a key role for TNF-alpha in the development of pre-eclampsia.