感染性早产患者血清、胎盘组织TNFRⅡ的表达水平及其与TNFRⅡ 196基因多态性的关系

Relationship Between the Levels of Maternal Serum sTNFR Ⅱ and the mRNA Expression of Placental TNFR Ⅱ in Preterm Labor with Chorioamnionitis and Polymorphism in-196 Site of Tumor Necrosis Factor-β Receptor Ⅱ

目的探讨肿瘤坏死因子α受体Ⅱ(TNFRⅡ)基因第6外显子196T→G多态性与早产合并绒毛膜羊膜炎遗传易感性的关系。方法对46例早产患者(根据胎盘病检有无绒毛膜羊膜炎分为早产感染组21例和早产非感染组25例)母血、胎盘组织和同期50例足月正常产母血、20例胎盘组织进行研究。应用RT-PCR技术测定胎盘组织中TNFRⅡmRNA的表达水平;采用ELISA法测定母血清可溶性TNFRⅡ(sTNFRⅡ)水平。采用PCR-限制性片段长度多态性(RFLP)对TNFRⅡ第6外显子196位点进行基因分型,分析该位点不同基因型间早产患者胎盘TNFRⅡmRNA和母血sTNFRⅡ水平的差异。结果①在早产患者中TNFRⅡ基因196位点TG(GG)基因型与TT基因型比较,其对应的TNFRⅡmRNA、sTNFRⅡ均有增高的趋势,但差异无统计学意义(P>0.05)。②孕妇胎盘组织中TNFRⅡmRNA及血清中sTNFRⅡ水平在早产感染组增高,差异有统计学意义(P<0.05),在早产非感染组和正常足月产组间差异无统计学意义(P>0.05)。早产组不同基因型与绒毛膜羊膜炎的相关性分析显示,TNFRⅡ基因TG+GG基因型与早产绒毛膜羊膜炎的发生可能相关(χ2=11.088,P<0.05),TG+GG基因型OR值为12.65,95%CI为2.359～67.848,其发生绒毛膜羊膜炎的几率是TT基因型的12.65倍。结论 TNFRⅡ基因第6外显子196位点突变不引起早产孕妇TNFRⅡ转录、翻译水平改变,该基因196位点多态性却与感染性早产孕妇血清sTNFRⅡ、胎盘组织TNFRⅡmRNA表达水平的增高有关,该位点多态性可以成为早期预测、诊断感染性早产的指标。

Objective To investigate the role of Tumor necrosis factor receptor Ⅱ （TNFR Ⅱ） in preterm labor with choriaamnionitis and their gene polyrnorphisms in genetic susceptibility to preterm labor with chorioamnionitis in Chengdu. Methods We collected 46 cases maternal serum and partial placental tissues of preterm labor （21 cases of infectious group with chorioamnionitis, 25 cases of noninfectious group without chorioamnionitis）, and 50 cases maternal serum and 20cases placental tissues of term labor in corresponding period. TNFR Ⅱ mRNA in placental tissue were tested by RT-PCR, maternal serum levels of sTNFR Ⅱ were measured by ELISA. According to preliminary studies on TNFR Ⅱ -196 site of the gene type, we analyze the sites of different genotypes in patients with premature placental TNFR Ⅱ rnRNA and maternal blood levels of sTNFR Ⅱ difference, and with different genotypes chorioamnionitis relevance. Results In patients with preterm labor, the results of placental TNFR Ⅱ mRNA and serum sTNFR Ⅱ were no statistically significant higher in TG （GG） than in TT （P〉0.05）. The levels of maternal serum sTNFR Ⅱ and the mRNA expression of placental TNFR Ⅱ in preterm labor with ehorioarnnionitis were significantly higher than those of preterm labor without chorioamnionitis and term labor （P 〈 0. 05）. There were no significant difference between term labor and preterm labor without chorioarnnionitis （P 〉 0. 05 ）. Close correlation was observed between the different genotypes and the chorioamnionitis（x2 =11. 088, P〈0.05）. The odds ratio （OR）for TG＋GG genotype was 12.65,95% CI 2. 359- 67. 848,with more than 12.65 times probability of chorioarnnionitis than that of TT genotype group. Conclusion It suggested that TNFR Ⅱ -196 polymorphism might not play a role by affecting TNFR Ⅱ production in preterm labor. The site polymorphism is associated with higher serum sTNFR Ⅱ and placenta TNFR Ⅱ mRNA expression in patient with chorioamnionitis. It can be a useful marker for early prediction and diagnosis of preterm labor with chorioamnionitis.