P1314 Immune Clusters and Ancestry-Associated Gene Expression in Chilean Ulcerative Colitis.

Abstract Background Ulcerative colitis (UC) is rising in South America, but regional genomic data are scarce. The Chilean population, with its mixed European and Mapuche ancestry, offers a distinctive model to explore ancestry-linked molecular patterns in UC. This study characterised the Chilean UC mucosal transcriptome profile. Methods Sigmoid mucosal biopsies from UC patients (n = 20; active = 9, inactive = 11) and healthy controls (n = 10) were analyzed by bulk RNA-seq using the Illumina NovaSeq6000. Differentially expressed genes were identified with DESeq2 (DEGs; FDR ≤ 0.05, |log2FC| > 1) and analysed for functional enrichment (GO and KEGG) as well as Protein–protein interaction topology (PPI, STRING v12.0). Immune-related clusters were defined using clusterProfiler. Gene expression was stratified by ancestry—Amerindian (>43%) or European—based on our prior IBD study (Sci Rep 2025; 15:15331). Results Significant DEGs were detected across all contrasts—active vs control (1,655), inactive vs control (22), and inactive vs active (535). KLF7 was the only DEG that was consistently altered across all disease states., which is a transcription factor linked to inflammatory pathways in visceral adipocytes. KLF7-associated genes included CTLA4, CXCL1, CXCL5, LIF, OSM, and PTGS2, suggesting a potential UC-related signature. Functional enrichment revealed three immune clusters: Cluster I involves leukocyte adhesion and activation, Cluster 2 reflects adaptive immune activation, and Cluster 3 highlights innate microbial sensing and inflammatory signaling. Furthermore, the PPI of the active UC network showed strong connectivity (235 nodes, 96 edges; p < 1 × 10⁻16) enriched for wound healing, angiogenesis, and ECM organization, whereas inactive UC displayed minimal coherence (20 nodes, 4 edges; p = 0.121). The active vs inactive comparison revealed dense network integration (230 nodes, 63 edges; p < 1 × 10⁻16), highlighting vascular and extracellular matrix remodeling processes. Lastly, analysis of ancestry proportion revealed increased expression of SA1009, CTLA4, CLDN8, CXCL11, and MMP3, suggesting a gene signature associated with Amerindian ancestry in UC. Conclusion KLF7 could be a potential biomarker, linked to proinflammatory genes. Active UC shows three immune clusters—leukocyte migration, adaptive, and innate responses. The PPI analysis reveals strong enrichment in wound healing, angiogenesis, cell migration, and ECM remodeling, highlighting vascular and ECM shifts as hallmarks of active disease. SA1009, CTLA4, CLDN8, CXCL11, and MMP3 correlate with Amerindian ancestry, suggesting ancestry-driven immune modulation and potential for tailored therapies in Chilean UC. References: Pérez-Jeldres T, Bustamante ML, Alvares D, et al. Impact of Amerindian ancestry on clinical outcomes in Crohn’s disease and ulcerative colitis in a Latino population. Sci Rep. 2025;15(1):15331. Wang C, Ha X, Li W, et al. Correlation of TLR4 and KLF7 in Inflammation Induced by Obesity. Inflammation. 2017;40(1):42-51. Zhang M, Wang C, Wu J, et al. The Effect and Mechanism of KLF7 in the TLR4/NF-κB/IL-6 Inflammatory Signal Pathway of Adipocytes. Mediators Inflamm. 2018;2018:1756494. Cao J, Ni Y, Zhang H, Ning X, Qi X. Inhibition of Kruppel-like factor 7 attenuates cell proliferation and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis through nuclear factor κB and mitogen-activated protein kinase signaling pathway. Exp Anim. 2022;71(3):356-367. Conflict of interest: Dr. Pérez, Tamara: No conflict of interest Valdes, Ivania: No conflict of interest Hernandez-Rocha, Cristian: No conflict of interest Ascui, Gabriel: No conflict of interest Segovia, Roberto: No conflict of interest Pavez, Carolina: No conflict of interest Candia, Roberto: No conflict of interest Hernandez, Elisa: No conflict of interest Silva, Veronica: No conflict of interest Arriagada Hernandez, Elizabeth: No conflict of interest Azocar, Lorena: No conflict of interest Miquel, Juan-Francisco: No conflict of interest Marki, Alex: No conflict of interest Riquelme, Erick: No conflict of interest Alvarez-lobos, Manuel: No Conflicts Sharma-Oates, Archana: No conflict of interest