rs7574865位点多态性与不明原因复发性自然流产相关的机制研究

Mechanism of unexplained recurrent spontaneous abortion associated with rs7574865 locus polymorphism

目的:探讨信号转导与转录激活因子4(STAT4)基因rs7574865位点多态性与不明原因复发性自然流产(URSA)的易感相关性及其不同基因型对STAT4表达的影响。方法:分别采用聚合酶链反应-限制性片段长度多态性法检测246例URSA患者和183名正常女性STAT4基因rs7574865位点的基因型分布;采用免疫组织化学技术测定86例URSA患者和77名正常女性蜕膜组织STAT4基因的蛋白表达。结果:rs7574865G/T基因型频率在URSA组和对照组中分别为G/G基因型36.2%、46.5%,G/T基因型47.2%、45.4%,T/T基因型16.2%、8.2%,两组基因型频率分布比较差异具有统计学意义(P<0.05),其中T等位基因明显增加URSA的发病风险(OR=1.51,P<0.05)。URSA组和对照组的蜕膜组织中STAT4基因蛋白表达量比较差异具有统计学意义(P<0.05)。URSA组内和对照组中,3种基因型的蜕膜组织STAT4蛋白存在明显的表达差异(P均<0.05),携带T/T基因型的蜕膜组织中STAT4蛋白高表达于G/G基因型(P均<0.05)。URSA组和对照组对应G/G、G/T和T/T三种基因型的STAT4蛋白的表达量比较差异均无统计学意义(P均>0.05)。结论:rs7574865位点多态性可能通过其危险基因型T/T增加STAT4基因在母体蜕膜组织的表达增加URSA患者的发病风险。

Objective： To investigate associations between the functional polymorphisms of signal transducer and activator of transcription 4 （ STAT4 ） gene and unexplained recurrent spontaneous abortion （URSA） between STAT4 protein expression and the genotypes of rs7574865 locus. Methods： PCR-restriction fragment length poly- morphism was used to genotype rs7574865 locus polymorphism in 246 URSA cases and 183 normal controls; immu- nohistochemical technique was used to detect STAT4 protein expression in 86 URSA cases and 77 normal controls. Results： The frequencies of rs7574865G/T were 36.2% , 46.5% in genotype G/G, 47.2% , 45.4% in genotype G/T and 16.2% , 8.2% in genotype T/T between URSA patients and normal controls, respectively. The distribu- tion of these two gene frequencies are significanty different （P 〈 0. 05 ）. The carriers of rs7574865T allele in- creased the risk of URSA （ OR = 1.51, P 〈 0. 05 ）. There was statistical difference in the STAT4 protein expression of decidual tissues between URSA group and control group （ P 〈 0.05 ）. In URSA patients there was statistical difference in the STAT4 protein expression among genotype GG, GT and TT of rs7574865 locus （ P 〈 0.05 ）. So was in normal control group （ P 〈 0. 05 ）. There was no difference in the STAT4 protein expression between geno- types and controls （ P 〉 0.05 ）. Neither was genotype GT and TT respectively （ all P 〉 0. 05 ）. Conclusion： Functional polymorphisms of the rs7574865 locus could probably confer the susceptibility to URSA via STAT4 pro- tein expression increased by genotype T/T in maternal decidual tissue.