MMPs基因多态性与延边地区未足月胎膜早破新生儿感染易感性的关系研究

In recent years, due to influence of society and environment, the incidence of preterm labor is increasing constantly, which is seriously affecting the new-born population’s qualification. Preterm premature rupture of membranes (PPROM) is one of the maijor risk factors leading preterm labor which occurs in 1/3. Also the incidence of PPROM shows racial differences,our previous study showed that the incidence of PPROM in Koreans of Yanbian area is 61.6 % which is significantly higher than those in Hans. Some studies reported that the genetic polymorphisms of matrix metalloproteinases(MMP) are association with the risk of PPROM.Infection and premature rupture of membranes(PROM) are mutually related to PPROM,individuals with both PPROM and infection will result in a higher morbidity and mortality.In this case-control study we will use Taqman method to analyze the MMPs genetic polymorphisms of Hans and Koreans in Yanbian area. We will further examine the relationships between PPROM and infection at molecular and protein levels.Investigating the effect of gene-environment interactions on the risk of PPROM will help identify the underlying pathways of PPROM in high- incidence population group of Koreans in Yanbian area. Moreover, this study will provide scientific evidence for determining the susceptible population of premature rupture of membranes and predicting the risk of infection of PPROM,early prevention and treatment strategies measures to improve its prognosis.

近年来，由于社会和环境因素的影响，早产的发生率逐年上升，严重影响出生人口素质。未足月胎膜早破（PPROM）是引起早产的主要原因，约占1/3。我们前期工作结果显示，延边地区朝鲜族PPROM发生率为61.6%，明显高于汉族，存在民族差异。研究表明，基质金属蛋白酶（MMPs）基因多态性与PPROM发生有密切关联，并存在地区和种族差异。感染与胎膜早破互为因果，特别是PPROM合并宫内感染新生儿因患病率和死亡率升高，备受关注。本课题以PPROM为切入点，利用病例-对照研究方法，应用iMLDR技术检测延边地区孕产妇感染相关基因位点的突变情况，并在分子及蛋白水平验证PPROM与感染相关性，同时结合PPROM高危因素，探讨基因-环境因素与PPROM新生儿感染易感性的关系，确定延边地区PPROM的易感人群，预测PPROM新生儿发生感染风险，制定早期防治措施，改善其预后提供科学依据。

随着环境和社会因素的影响，早产儿的发生率逐年增高。由早产所致的围生儿发病率、病死率以及后遗症问题已成为一个世界性的卫生问题。未足月胎膜早破（PPROM）是早产的重要原因，感染与胎膜早破互为因果，已得到专家共识，但何种遗传背景和环境的相互作用及其机制尚未明确。我们前期工作结果显示，延边地区朝鲜族PPROM发生率为61.6%，明显高于汉族，存在民族差异。本课题基于前期数据，研究延边地区人群胎膜早破流行病学及人群的遗传背景特征研究，深入了解早产、胎膜早破、新生儿感染易感性与基因多态性之间的关系。通过iMLDR技术检测延边地区胎膜早破相关基因位点的突变情况，并在分子及蛋白水平验证sTREM-1、IL-6、TLR2、TLR4、MCP-1及MMPs 等炎症指标与PPROM、感染相关性。结果得出以下结论：1)胎盘组织中MMP-1、MMP-8、MMP-9、HMGB1及TLR-2、4的高水平与PPROM密切相关；2)脐带血MMP-9、MMP-1及MCP-1高水平与PPROM合并绒毛膜羊膜炎有关；3)脐带血中sTREM-1和pro-ADM水平可早期预测PPROM合并新生儿感染；4)MMP-9rs3918242单核苷酸基因多态性与PPROM有关，C等位基因可能是PPROM的保护性基因，T等位基因可能是PPROM的风险性基因；5）PPROM组胎盘组织中Nrf2、HO-1及NQO1蛋白水平低表达与PPROM相关,提示抗氧化损伤是未来预防PPROM的方向之一。本课题为确定延边地区PPROM的易感人群，预测PPROM新生儿发生感染风险，制定早期有效防治措施，改善其预后提供一定科学依据。