PDF | https://doi.org/10.46613/congastro2023-59
This work is licensed under CC BY 4.0
Perez T1, Bustamante M2, Aguilar N1, Baez P2, Magne F2, Hernandez C1, Azocar L1, Estela R3, Escobar S3, Zazueta A2, De la Vega A3, Arriagada E3, Silva V3, Pavez C1, Candia R1, Onetto G3, Gonzalez M3, Segovia R4, Miquel J1, Alvarez M1, Alvarez D5
1Pontificia Universidad Católica, Santiago, Chile
2Universidad de Chile, Santiago, Chile
3Hospital San Borja, Santiago, Chile
4Red Salud Arauco, Santiago, Chile
5University of Cambridge, Cambridge, Unión Europea
…
Background: IBD genetics research has primarily focused on Causasian populations, resulting in underrepresentation of Latin populations in these studies. Method: 192 Chilean individuals with IBD (145 UC and 47 CD) were genotyped using Illumina GSA Arrays. From IBD GWAS (Jostin et al. and Liu et al.), we selected gene variants related to IBD. Then, we built a Chilean dataset (clinical-genotype information). Using this dataset, we performed a Spearman correlation matrix to correlate clinical outcomes with IBD variants. Further, we built regression models to predict the clinical outcomes using the variants obtained from the correlation matrix (p <0.05). The best models were selected using significance testing or likelihood-based information criterion, such as the Akaike Information Criterion (AIC), and plotted using a Receiver Operating Characteristic Curve (ROC). Finally, to evaluate the association among variants in each model, we perform a Gene Ontology biological process enrichment analysis using PANTHER (Fisher, FDR). Results. As shown in Figure 1, the best predictive regression models (more than 80%) for the clinical outcomes were surgery, clinical/endoscopy remission for more than five years, and naïve anti-TNF. Association with genetic variants was observed significantly (p<0.05) in the enrichment analysis for the model Clinical/endoscopy remission of more than five years. Finally, for each variant in this model, a Chi-square test was conducted to determine whether there was a significant difference among patients genotypes in terms of clinical/endoscopic prolonged remission outcome (yes/no). The analysis revealed significant differences for the following variants: rs6837335, rs11742570, rs7134599, and rs6142618. Conclusion. Candidates’ genes related to clinical outcomes in our Chilean IBD cohort were related to epithelial, innate, and adaptative immune responses and host-microbial interactions. Future research is needed to validate these findings.
