Browsing by Author "Silva, Veronica"

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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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    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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    Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors
    (IMPACT JOURNALS LLC, 2016) Lobos Gonzalez, Lorena; Silva, Veronica; Araya, Mariela; Restovic, Franko; Echenique, Javiera; Oliveira Cruz, Luciana; Fitzpatrick, Christopher; Briones, Macarena; Villegas, Jaime; Villota, Claudio; Vidaurre, Soledad; Borgna, Vincenzo; Socias, Miguel; Valenzuela, Sebastian; Lopez, Constanza; Socias, Teresa; Varas, Manuel; Diaz, Jorge; Burzio, Luis O.; Burzio, Veronica A.
    We reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10 cell proliferation and induces apoptosis in vitro through downregulation of pro-survival and metastasis markers, particularly survivin. For in vivo studies, subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically with specific and control antisense oligonucleotides (ASO). For metastasis studies, tumors were resected, followed by systemic administration of ASOs and the presence of metastatic nodules in lungs and liver was assessed. Treatment with specific ASO inhibited tumor growth and metastasis after primary tumor resection. In a metastasis-only assay, mice inoculated intravenously with cells and treated with the same ASO displayed reduced number and size of melanoma nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs are the first potential non-nuclear targets for melanoma therapy.