Identification of hub genes in placental dysfunction and recurrent pregnancy loss through transcriptome data mining: A meta-analysis.

Recurrent pregnancy loss (RPL) is a condition characterized by the loss of two or more pregnancies before 20 weeks of gestation. The causes of RPL are complex and can be due to a variety of factors, including genetic, immunological, hormonal, and environmental factors. This transcriptome data mining study was done to explore the differentially expressed genes (DEGs) and related pathways responsible for pathogenesis of RPL using an Insilco approach. RNAseq datasets from the Gene Expression Omnibus (GEO) database was used to extract RNAseq datasets of RPL. Meta-analysis was done by ExpressAnalyst. The functional and pathway enrichment analysis of DEGs were performed using KEGG and BINGO plugin of Cytoscape software. Protein-protein interaction was done using STRING and hub genes were identified. A total of 91 DEGs were identified, out of which 10 were downregulated and 81 were upregulated. Pathway analysis indicated that majority of DEGs were enriched in immunological pathways (IL-17 signalling pathway, TLR-signalling pathway, autoimmune thyroid disease), angiogenic VEGF-signalling pathway and cell-cycle signalling pathways. Of these, 10 hub genes with high connectivity were selected (CXCL8, CCND1, FOS, PTGS2, CTLA4, THBS1, MMP2, KDR, and CD80). Most of these genes are involved in maintenance of immune response at maternal-fetal interface. Further, in functional enrichment analyses revealed the highest node size in regulation of biological processes followed by cellular processes, their regulation and regulation of multicellular organismal process. This in-silico transcriptomics meta-analysis findings could potentially contribute in identifying novel biomarkers and therapeutic targets for RPL, which could lead to the development of new diagnostic and therapeutic strategies for this condition.

Estrogen Receptor 1 Gene Polymorphism and its Association with Idiopathic Short Stature in a North Indian Population

Objective: In the hypothalamic-pituitary-gonadotrophin axis, estrogen plays a key role in the regulation of bone maturation and growth plate closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in a North Indian population. Methods: Four SNPs of ESR1 (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in ISS patients and controls. Linkage disequilibrium (LD) and haplotyping were done by SNPStat and SHEsisPlus software. The extent of LD was determined by calculating D' and R2 values in SNP paired combinations. Results: Fifty-two ISS patients were compared with 68 controls. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility. The frequencies of the rs6557177 CC genotype [p=0.030; odds ratio (OR)=0.13; 95% confidence interval (CI): 0.01-1.10] and rs543650 genotype TT (p=0.043; OR=0.29; 95% CI: 0.09-0.92) were increased in the ISS group compared with controls. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 showed strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799. Conclusion: Our study showed that the CC genotype at rs6557177 and TT genotype at rs543650 of ESR1 constituted a risk factor for developing ISS in North Indian children. These findings may lead to a better understanding of the SNPs associated with ISS susceptibility.