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Background Genome-wide association studies (GWAS) have identified hundreds of polymorphisms associated with an increased risk of developing IBD. Among risk genes identified by GWAS, CARD9, a gene encoding an adapter molecule involved in the innate immune response to fungi and bacteria, has been related to IBD risk. CARD9 alleles in IBD patients may have either a protective function or a high genetic risk factor such as rs4077515. Interestingly, the CARD9S12N (rs4077515) variant has a higher frequency in the Latin South American population than the Caucasian population. The relevance of rs4077515 in the risk of IBD in the Latino population is unknown. Aims (1) To estimate allele and genotype frequencies for rs4077515 in IBD patients and Chilean controls and compare with Ensembl genome database (public data available). (2) To compare the allele and genotype distributions in IBD patients and controls, including association tests and estimation of ORs according to additive, dominant and recessive penetrance models. Methods 260 IBD patients were genotyped using the TaqMan SNP genotyping technology based on qPCR. Aggregated genotype information for 3147 population-based Chilean controls was retrieved from a published study on gallstones in Chileans (Lorenzo et al., Hepatology 2021). We calculated the allele and genotype frequencies for rs4077515 and then compared these frequencies with controls. A Chi-square test of association was used under the null hypothesis of no association between genotypes and disease. Univariate and multiple logistic regression were performed (additive, dominant, and recessive penetrance models). Results Table 1 compares rs4077515 allele and genotype frequencies in Chileans and other populations (Ensembl data set). Table 2. exhibits the estimated odds ratio for IBD, CD, and UC in Chilean population. Table 3. reveals the association results for rs4077151 models in the Chilean population. Conclusion In this study, the A risk allele for rs4077515 is significantly more frequent in the Chilean population than reported in other populations such as European, but similar to Amerindian. In this Chilean cohort, the variant rs4077515 is not associated with higher IBD risk. However, this could be an effect of sample size, or patients carrying rs4077515 requires an additional factor to IBD development.

Background IBD has emerged as a worldwide disease with an increased incidence in newly industrialized countries such as Chile. This population has been underrepresented in genome-wide association studies (GWAS) because IBD genetics studies have focused mainly on North America and European populations. In addition, specific IBD risk alleles have been related to different races and ethnicities. Aim: To investigate the association of IBD risk variants reported in previous GWAS studies with clinical outcomes in our Chilean patients. Methods 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 with pGWAS value < 5x10-8 and looked for them in our Chilean IBD group. 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). Then, we selected the best models using significance testing (P values) or likelihood-based information criterion, such as the Akaike Information Criterion (AIC) and plotted the models 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 and Table 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 (Table 2). Conclusion 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.

Background Most genetic association studies rely on Caucasian, African and Asian individuals with inconsistent results depending on the population investigated, suggesting that genetic susceptibility to inflammatory bowel disease (IBD) may depend on interactions between ethnicity and genetic-environmental factors. Aim: To explore the contribution of genetic ancestry to IBD risk in Chileans. Aim: To explore the contribution of genetic ancestry to IBD risk in Chileans. Methods 192 Chilean IBD patients were genotyped using Illumina’s Global Screening Array. Genotype data was combined with similar information from 3147 population-based Chilean controls from a published study on gallstones, body mass index, c-reactive protein and gallbladder cancer in Chileans (Barahona et al., Hepatology 2021). The individual proportions of Aymara, African, European and Mapuche ancestry were estimated using the software ADMIXTURE (supervised estimation). Using the statistical software R version 4.2.1, we calculated the odds ratios (OR) and 95% confidence intervals (CI) for gender, as well as age and ancestry proportions grouped into quartiles using the library "epitools". Results Table 1 shows the investigated characteristics of the study population and their association with IBD risk. For example, the 1st and 3rd quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7% and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52-3.48) for the lowest versus the highest group. Conclusion The type and proportion of Native American ancestry in Chileans seems to be associated with IBD risk.

Background: A Few preclinical studies have shown that Knee osteoarthritis (KOA) is linked to gut microbiome dysbiosis and chronic inflammation. This pilot study was designed to look at the gut microbiome composition in KOA patients and normal individuals with or without vitamin D deficiency (VDD, serum vitamin D <30 ng/ml). Methods: This pilot study was conducted prospectively in 24 participants. The faecal samples of all the participants were taken for DNA extraction. The V3-V4 region of 16s rRNA was amplified and the library was prepared and sequenced on the Illumina Miseq platform. Results: The mean (±SD) age was 45.5 (±10.2) years with no defined co-morbidities. Of 447 total Operational Taxonomic Units (OTUs), a differential abundance of 16 nominally significant OTUs between the groups were observed. Linear discriminate analysis (LEfSe) revealed a significant difference in bacteria among the study groups. Pseudobutyrivibrio and Odoribacter were specific for VDD while Parabacteroides, Butyricimonas, and Gordonibacter were abundant in the KOA_VDD group and Peptococcus, Intestimonas, Delftia, and Oribacterium were abundant in the KOA group. About 80% of bacterial species were common among different groups and hence labeled as core bacterial species. However, the core microbiome of KOA and VDD groups were not seen in the KOA_VDD group, suggesting that these bacterial groups were affected by the interaction of the KOA and VDD factors. Conclusion: Parabacteroides, Butyricimonas, Pseudobutyrivibrio, Odoribacter, and Gordonibacter are the predominant bacteria in vitamin D deficient patients with or without KOA. Together these results indicate an association between the gut microbiome, vitamin D, and knee osteoarthritis.