Saadaty Aida, Parhoudeh Sara, Khashei Varnamkhasti Khalil, Moghanibashi Mehdi, Naeimi Sirous
Department of Genetics, College of Science, Kazerun Branch, Islamic Azad University, Kazerun 73, Iran.
Department of Medical Laboratory Sciences, Faculty of Medicine, Kazerun Branch, Islamic Azad University, Kazerun 73, Iran.
Biomedicines. 2023 Apr 24;11(5):1257. doi: 10.3390/biomedicines11051257.
The early diagnosis of preeclampsia, a key outlook in improving pregnancy outcomes, still remains elusive. The present study aimed to examine the interleukin-13 and interleukin-4 pathway potential in the early detection of preeclampsia as well as the relationship between interleukin-13 rs2069740(T/A) and rs34255686(C/A) polymorphisms and preeclampsia risk to present a combined model. This study utilized raw data from the GSE149440 microarray dataset, and an expression matrix was constructed using the RMA method and affy package. The genes related to the interleukin-13 and interleukin-4 pathway were extracted from the GSEA, and their expression levels were applied to design multilayer perceptron and PPI graph convolutional neural network models. Moreover, genotyping for the rs2069740(T/A) and rs34255686(C/A) polymorphisms of the interleukin-13 gene were tested using the amplification refractory mutation system PCR method. The outcomes revealed that the expression levels of interleukin-4 and interleukin-13 pathway genes could significantly differentiate early preeclampsia from normal pregnancy. Moreover, the present study's data suggested significant differences in the genotype distribution, the allelic frequencies and some of the risk markers of the study, in the position of rs34255686 and rs2069740 polymorphisms between the case and control groups. A combined test of two single nucleotide polymorphisms and an expression-based deep learning model could be designed for future preeclampsia diagnostic purposes.
子痫前期的早期诊断是改善妊娠结局的关键,但仍然难以实现。本研究旨在探讨白细胞介素-13和白细胞介素-4通路在子痫前期早期检测中的潜力,以及白细胞介素-13 rs2069740(T/A)和rs34255686(C/A)多态性与子痫前期风险之间的关系,以提出一个联合模型。本研究利用了GSE149440微阵列数据集的原始数据,并使用RMA方法和affy软件包构建了表达矩阵。从GSEA中提取与白细胞介素-13和白细胞介素-4通路相关的基因,并将其表达水平应用于设计多层感知器和PPI图卷积神经网络模型。此外,使用扩增阻滞突变系统PCR方法检测白细胞介素-13基因rs2069740(T/A)和rs34255686(C/A)多态性的基因分型。结果显示,白细胞介素-4和白细胞介素-13通路基因的表达水平能够显著地区分子痫前期早期与正常妊娠。此外,本研究的数据表明,病例组和对照组之间在rs34255686和rs2069740多态性位点的基因型分布、等位基因频率以及本研究的一些风险标志物存在显著差异。可以设计一种将两个单核苷酸多态性与基于表达的深度学习模型相结合的检测方法,用于未来子痫前期的诊断。