Multi-Omics Analysis Revealed the rSNPs Potentially Involved in T2DM Pathogenic Mechanism and Metformin Response.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39273245", "kind": "science-record", "revision": 3, "content_hash": "sha256:ba716a297ac14b41d1fd053d9a97ea9dc6f6d0be17fac769c190b2d067ab5abf", "created_at": "2026-11-01T20:29:26Z", "updated_at": "2026-11-01T22:12:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Multi-Omics Analysis Revealed the rSNPs Potentially Involved in T2DM Pathogenic Mechanism and Metformin Response.", "doi": "10.3390/ijms25179297", "pmid": "39273245", "authors": ["Igor S Damarov", "Elena E Korbolina", "Elena Y Rykova", "Tatiana I Merkulova"], "journal": "International journal of molecular sciences", "year": 2024, "abstract": "The goal of our study was to identify and assess the functionally significant SNPs with potentially important roles in the development of type 2 diabetes mellitus (T2DM) and/or their effect on individual response to antihyperglycemic medication with metformin. We applied a bioinformatics approach to identify the regulatory SNPs (rSNPs) associated with allele-asymmetric binding and expression events in our paired ChIP-seq and RNA-seq data for peripheral blood mononuclear cells (PBMCs) of nine healthy individuals. The rSNP outcomes were analyzed using public data from the GWAS (Genome-Wide Association Studies) and Genotype-Tissue Expression (GTEx). The differentially expressed genes (DEGs) between healthy and T2DM individuals (GSE221521), including metformin responders and non-responders (GSE153315), were searched for in GEO RNA-seq data. The DEGs harboring rSNPs were analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We identified 14,796 rSNPs in the promoters of 5132 genes of human PBMCs. We found 4280 rSNPs to associate with both phenotypic traits (GWAS) and expression quantitative trait loci (eQTLs) from GTEx. Between T2DM patients and controls, 3810 rSNPs were detected in the promoters of 1284 DEGs. Based on the protein-protein interaction (PPI) network, we identified 31 upregulated hub genes, including the genes involved in inflammation, obesity, and insulin resistance. The top-ranked 10 enriched KEGG pathways for these hubs included insulin, AMPK, and FoxO signaling pathways. Between metformin responders and non-responders, 367 rSNPs were found in the promoters of 131 DEGs. Genes encoding transcription factors and transcription regulators were the most widely represented group and many were shown to be involved in the T2DM pathogenesis. We have formed a list of human rSNPs that add functional interpretation to the T2DM-association signals identified in GWAS. The results suggest candidate causal regulatory variants for T2DM, with strong enrichment in the pathways related to glucose metabolism, inflammation, and the effects of metformin.", "claims": [{"id": "claim-method", "statement": "Allelic asymmetry for all heterozygous positions in the ChIP-seq and RNA-seq data was computed using the binomial test against the null hypothesis on an equal coverage of heterozygous positions by the reference reads aligned to reference genome and the alternative reads aligned to alternative genome with subsequent correction for multiple comparison according to Benjamini–Hochberg (p.adj. < 0.1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39273245", "locator": "sections[19] \"4.8. 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