Mohamad Muhammad Aliff, Mohd Manzor Nur Fariha, Zulkifli Noor Fadzilah, Zainal Nurzaireena, Hayati Abd Rahman, Ahmad Asnawi Asral Wirda
Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Kuala Lumpur 56100, Selangor, Malaysia.
Department of Obstetrics and Gynaecology, Hospital Ampang, Ampang Jaya 68000, Selangor, Malaysia.
Biology (Basel). 2020 Mar 27;9(4):62. doi: 10.3390/biology9040062.
Preeclampsia is a pregnancy-specific disorder characterized by the presence of hypertension with the onset of either proteinuria, maternal organ or uteroplacental dysfunction. Preeclampsia is one of the leading causes of maternal and fetal mortality and morbidity worldwide. However, the etiopathologies of preeclampsia are not fully understood. Many studies have indicated that genes are differentially expressed between normal and in the disease state. Hence, this study systematically searched the literature on human gene expression that was differentially expressed in preeclampsia. An electronic search was performed through 2019 through PubMed, Scopus, Ovid-Medline, and Gene Expression Omnibus where the following MeSH (Medical Subject Heading) terms were used and they had been specified as the primary focus of the articles: Gene, placenta, preeclampsia, and pregnancy in the title or abstract. We also found additional MeSH terms through Cochrane Library: Transcript, sequencing, and profiling. From 687 studies retrieved from the search, only original publications that had performed high throughput sequencing of human placental tissues that reported on differentially expressed genes in pregnancies with preeclampsia were included. Two reviewers independently scrutinized the titles and abstracts before examining the eligibility of studies that met the inclusion criteria. For each study, study design, sample size, sampling type, and method for gene analysis and gene were identified. The genes listed were further analyzed with the DAVID, STRING and Cytoscape MCODE. Three original research articles involving preeclampsia comprising the datasets in gene expression were included. By combining three studies together, 250 differentially expressed genes were produced at a significance setting of < 0.05. We identified candidate genes: LEP, NRIP1, SASH1, and ZADHHC8P1. Through GO analysis, we found extracellular matrix organization as the highly significant enriched ontology in a group of upregulated genes and immune process in downregulated genes. Studies on a genetic level have the potential to provide new insights into the regulation and to widen the basis for identification of changes in the mechanism of preeclampsia. Integrated bioinformatics could identify differentially expressed genes which could be candidate genes and potential pathways in preeclampsia that may improve our understanding of the cause and underlying molecular mechanisms that could be used as potential biomarkers for risk stratification and treatment.
子痫前期是一种妊娠特有的疾病，其特征为高血压，并伴有蛋白尿、母体器官或子宫胎盘功能障碍。子痫前期是全球孕产妇和胎儿死亡及发病的主要原因之一。然而，子痫前期的病因尚未完全明确。许多研究表明，正常状态与疾病状态下基因的表达存在差异。因此，本研究系统检索了关于子痫前期中差异表达的人类基因表达的文献。通过PubMed、Scopus、Ovid-Medline和基因表达综合数据库进行了截至2019年的电子检索，使用了以下医学主题词（MeSH），并将其指定为文章的主要重点：标题或摘要中的基因、胎盘、子痫前期和妊娠。我们还通过考克兰图书馆找到了其他MeSH词：转录本、测序和分析。从检索到的687项研究中，仅纳入了对人类胎盘组织进行高通量测序并报告子痫前期妊娠中差异表达基因的原始出版物。两名评审员在审查符合纳入标准的研究的合格性之前，先独立审查了标题和摘要。对于每项研究，确定了研究设计、样本量、采样类型以及基因分析方法和基因。使用DAVID、STRING和Cytoscape MCODE对列出的基因进行了进一步分析。纳入了三篇涉及子痫前期基因表达数据集的原始研究文章。将三项研究合并后，在显著性设定为<0.05时产生了250个差异表达基因。我们确定了候选基因：LEP、NRIP1、SASH1和ZADHHC8P1。通过基因本体（GO）分析，我们发现细胞外基质组织是一组上调基因中高度显著富集的本体，而免疫过程是下调基因中高度显著富集的本体。基因水平的研究有可能为调节提供新见解，并拓宽子痫前期发病机制变化的识别基础。综合生物信息学可以识别差异表达基因，这些基因可能是子痫前期的候选基因和潜在途径，这可能会增进我们对病因和潜在分子机制的理解，这些机制可用作风险分层和治疗的潜在生物标志物。
