Pereyra Silvana, Bertoni Bernardo, Sapiro Rossana
Departamento de Genética, Facultad de Medicina, Universidad de la República, Av. General Flores 2125, C.P. 11800 Montevideo, Uruguay.
Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Av. General Flores 2125, C.P. 11800 Montevideo, Uruguay.
Eur J Obstet Gynecol Reprod Biol. 2016 Jul;202:20-5. doi: 10.1016/j.ejogrb.2016.04.030. Epub 2016 Apr 29.
Preterm birth (PTB) is a complex disease in which medical, social, cultural, and hereditary factors contribute to the pathogenesis of this adverse event. Interactions between genes and environmental factors may complicate our understanding of the relative influence of both effects on PTB. To overcome this, we combined data obtained from a cohort of newborns and their mothers with multiplex analysis of inflammatory-related genes and several environmental risk factors of PTB to describe the environmental-genetic influence on PTB.
The study aimed to investigate the association between maternal and fetal genetic variations in genes related to the inflammation pathway with PTB and to assess the interaction between environmental factors with these variations.
We conducted a case-control study at the Pereira Rossell Hospital Center, Montevideo, Uruguay. The study included 143 mother-offspring dyads who delivered at preterm (gestational age<37 weeks) and 108 mother-offspring dyads who delivered at term. We used real-time PCR followed by a high-resolution melting analysis to simultaneously identify gene variations involved in inflammatory pathways in the context of environmental variables. The genes analyzed were: Toll-like receptor 4 (TLR4), Interleukin 6 (IL6), Interleukin 1 beta (IL1B) and Interleukin 12 receptor beta (IL12RB).
We detected a significant interaction between IL1B rs16944 polymorphism in maternal samples and IL6 rs1800795 polymorphism in newborns, emphasizing the role of the interaction of maternal and fetal genomes in PTB. In addition, smoke exposure and premature rupture of membranes (PROM) were significantly different between the premature group and controls. IL1B and IL6 polymorphisms in mothers were significantly associated with PTB when controlling for smoke exposure. TLR4 polymorphism and PROM were significantly associated with PTB when controlling for PROM, but only in the case of severe PTB.
Interactions between maternal and fetal genomes may influence the timing of birth. By incorporating environmental data, we revealed genetic associations with PTB, a finding not found when we analyzed genetic data alone. Our results stress the importance of studying the effect of genotype interactions between mothers and children in the context of environmental factors because they substantially contribute to phenotype variability.
早产是一种复杂的疾病，其中医学、社会、文化和遗传因素都对这一不良事件的发病机制有影响。基因与环境因素之间的相互作用可能使我们难以理解两者对早产的相对影响。为了克服这一问题，我们将从一组新生儿及其母亲那里获得的数据与炎症相关基因的多重分析以及早产的几个环境风险因素相结合，以描述环境 - 基因对早产的影响。
本研究旨在调查与炎症途径相关基因中母体和胎儿基因变异与早产之间的关联，并评估环境因素与这些变异之间的相互作用。
我们在乌拉圭蒙得维的亚的佩雷拉·罗塞尔医院中心进行了一项病例对照研究。该研究包括143对早产（孕周<37周）的母婴二元组和108对足月分娩的母婴二元组。我们使用实时聚合酶链反应（PCR），随后进行高分辨率熔解分析，以在环境变量的背景下同时识别参与炎症途径的基因变异。分析的基因包括：Toll样受体4（TLR4）、白细胞介素6（IL6）、白细胞介素1β（IL1B）和白细胞介素12受体β（IL12RB）。
我们在母体样本中的IL1B rs16944多态性与新生儿中的IL6 rs1800795多态性之间检测到显著的相互作用，强调了母体和胎儿基因组相互作用在早产中的作用。此外，早产组和对照组之间的吸烟暴露和胎膜早破（PROM）存在显著差异。在控制吸烟暴露时，母亲中的IL1B和IL6多态性与早产显著相关。在控制胎膜早破时，TLR4多态性和胎膜早破与早产显著相关，但仅在严重早产的情况下。
母体和胎儿基因组之间的相互作用可能影响分娩时间。通过纳入环境数据，我们揭示了与早产相关的基因关联，这是我们单独分析基因数据时未发现的结果。我们的结果强调了在环境因素背景下研究母婴基因型相互作用影响的重要性，因为它们对表型变异有很大贡献。
