Browsing by Author "Estela, Ricardo"

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    Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort
    (2023) Pérez Jeldres, Tamara De Lourdes; Magne, Fabien; Ascui, Gabriel; Alvares, Danilo; Orellana, Matias; Álvarez Lobos Manuel Marcelo; Hernández Rocha, Cristián Antonio; Azocar, Lorena; Aguilar, Nataly; Espino, Alberto; Estela, Ricardo; Escobar, Sergio; Zazueta, Alejandra; Baez, Pablo; Silva, Veronica; de la Vega, Andres; Arriagada, Elizabeth; Pávez Ovalle, Carolina Denisse; Diaz-Asencio, Alejandro; Travisany, Dante; Miquel Poblete, Juan Francisco; Villablanca, Eduardo J.; Kronenberg, Mitchell; Bustamante, Maria Leonor
    Background and aimsLatin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort.MethodsA total of 192 Chilean IBD patients were genotyped using Illumina's Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry.ResultsThe first and third 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 vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells.ConclusionThe type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response.
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    Ethnicity influences phenotype and clinical outcomes: Comparing a South American with a North American inflammatory bowel disease cohort
    (2022) Perez-Jeldres, Tamara; Pizarro, Benjamin; Ascui, Gabriel; Orellana, Matias; Cerda-Villablanca, Mauricio; Alvares, Danilo; de la Vega, Andres; Cannistra, Macarena; Cornejo, Barbara; Baez, Pablo; Silva, Veronica; Arriagada, Elizabeth; Rivera-Nieves, Jesus; Estela, Ricardo; Hernandez-Rocha, Cristian; alvarez-Lobos, Manuel; Tobar, Felipe
    Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD), has emerged as a global disease with an increasing incidence in developing and newly industrialized regions such as South America. This global rise offers the opportunity to explore the differences and similarities in disease presentation and outcomes across different genetic backgrounds and geographic locations. Our study includes 265 IBD patients. We performed an exploratory analysis of the databases of Chilean and North American IBD patients to compare the clinical phenotypes between the cohorts. We employed an unsupervised machine-learning approach using principal component analysis, uniform manifold approximation, and projection, among others, for each disease. Finally, we predicted the cohort (North American vs Chilean) using a random forest. Several unsupervised machine learning methods have separated the 2 main groups, supporting the differences between North American and Chilean patients with each disease. The variables that explained the loadings of the clinical metadata on the principal components were related to the therapies and disease extension/location at diagnosis. Our random forest models were trained for cohort classification based on clinical characteristics, obtaining high accuracy (0.86 = UC; 0.79 = CD). Similarly, variables related to therapy and disease extension/location had a high Gini index. Similarly, univariate analysis showed a later CD age at diagnosis in Chilean IBD patients (37 vs 24; P = .005). Our study suggests a clinical difference between North American and Chilean IBD patients: later CD age at diagnosis with a predominantly less aggressive phenotype (39% vs 54% B1) and more limited disease, despite fewer biological therapies being used in Chile for both diseases.
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    Genotype Prevalence of Lactose Deficiency, Vitamin D Deficiency, and the Vitamin D Receptor in a Chilean Inflammatory Bowel Disease Cohort: Insights from an Observational Study
    (MDPI, 2023) Pérez Jeldres, Tamara De Lourdes; Bustamante, M. Leonor; Segovia-Melero, Roberto; Aguilar, Nataly; Magne, Fabien; Ascui, Gabriel; Uribe, Denisse; Azocar, Lorena; Hernández Rocha, Cristián Antonio; Estela, Ricardo; Silva, Veronica; De La Vega, Andres; Arriagada, Elizabeth; Gonzalez, Mauricio; Onetto, Gian-Franco; Escobar, Sergio; Baez, Pablo; Zazueta, Alejandra; Pávez Ovalle Carolina Denisse; Miquel Poblete, Juan Francisco; Álvarez Lobos Manuel Marcelo
    Lactose intolerance (LI) and vitamin D deficiency (VDD) have been linked to inflammatory bowel disease (IBD). We conducted an observational study in 192 Chilean IBD patients to investigate the prevalence of a specific gene variant (LCT-13910 CC genotype) associated with LI and the prevalence of VDD/Vitamin D Receptor (VDR) gene variants. Blood samples were analyzed using Illumina's Infinium Global Screening Array. The LCT-13910 CC genotype was found in 61% of IBD patients, similar to Chilean Hispanic controls and lower than Chilean Amerindian controls. The frequency of the LCT-13910-C allele in Chilean IBD patients (0.79) was comparable to the general population and higher than Europeans (0.49). Regarding VDR and VDD variants, in our study, the rs12785878-GG variant was associated with an increased risk of IBD (OR = 2.64, CI = 1.61-4.32; p-value = 0.001). Sixty-one percent of the Chilean IBD cohort have a genetic predisposition to lactose malabsorption, and a significant proportion exhibit genetic variants associated with VDD/VDR. Screening for LI and VDD is crucial in this Latin American IBD population.
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    Impact of Amerindian ancestry on clinical outcomes in Crohn’s disease and ulcerative colitis in a Latino population
    (2025) Pérez Jeldres, Tamara De Lourdes; Bustamante, María Leonor; Álvares, Danilo; Álvarez Lobos, Manuel Marcelo; Kalmer, Lajos; Azócar López, Lorena Karina; Segovia Melero, Roberto; Ascui, Gabriel; Aguilar, Nataly; Estela, Ricardo; Hernández Rocha, Cristian Antonio; Candia Balboa, Roberto Andrés; González, Mauricio; Silva, Verónica; De La Vega, Andrés; Arriagada, Elizabeth; Serrano, Carolina A.; Pávez Ovalle, Carolina Denisse; Quinteros Moraga, Carol; Miquel Poblete, Juan Francisco; Alex, Di Genova
    Research in Inflammatory Bowel Disease (IBD) assessing the genetic structure and its association with IBD phenotypes is needed, especially in IBD-underrepresented populations such as the South American IBD population. Aim. We examine the correlation between Amerindian ancestry and IBD phenotypes within a South American cohort and investigate the association between previously identified IBD risk variants and phenotypes. We assessed the ancestral structure (IBD = 291, Controls = 51) to examine the association between Amerindian ancestry (AMR) and IBD variables. Additionally, we analyzed the influence of known IBD genetic risk factors on disease outcomes. We used Chi-square and Fisher’s tests to analyze the relationship between phenotypes and ancestry proportions, calculating odds ratios (OR) and confidence intervals (CI). Logistic regression examined genetic variants associations with IBD outcomes, and classification models for predicting prolonged remission were developed using decision tree and random forest techniques. The median distribution of global ancestry was 58% European, 39% Amerindian, and 3% African. There were no significant differences in IBD risk based on ancestry proportion between cases and controls. In Ulcerative colitis (UC), patients with a high Amerindian Ancestry Proportion (HAAP) were significantly linked to increased chances of resective surgery (OR = 4.27, CI = 1.41–12.94, p = 0.01), pouch formation (OR = 7.47, CI = 1.86–30.1, p = 0.003), and IBD reactivation during COVID-19 infection (OR = 5.16, CI = 1.61–6.53, p = 0.005). Whereas, in the Crohn’s Disease (CD) group, the median Amerindian ancestry proportion was lower in the group with perianal disease (33.5% versus 39.5%, P value = 0.03). CD patients with High Amerindian Ancestry proportion had lower risk for surgery (OR = 0.17, CI = 0.03–0.83, P value = 0.02). Our study highlights the impact of Amerindian ancestry on IBD phenotypes, suggesting a role for genetic and ancestral factors in disease phenotype. Further investigation is needed to unravel the underlying mechanisms driving these associations.