Browsing by Author "Galindo Muñoz, Karen Melissa"

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    Asociación entre niveles séricos de bilirrubina, variantes genéticas en UGT1A1 e hígado graso no-alcohólico en adolescentes de la cohorte chilena “Estudio de crecimiento y obesidad”
    (2023) Galindo Muñoz, Karen Melissa; Santos Martín, José Luis; Gana Ansaldo, Juan Cristóbal; Pontificia Universidad Católica de Chile. Escuela de Medicina
    Introducción: La bilirrubina es una molécula resultante de la degradación del grupo hemo, y que es conjugada en el hígado con ácido glucurónico por la enzima UGT1A1 (uridina difosfato glucuroniltransferasa 1A1) dando lugar a bilirrubina conjugada. Junto al incremento de la prevalencia de obesidad a lo largo de la vida, se ha observado un avance en la frecuencia de acumulación de grasa intrahepática que progresa a enfermedad de hígado graso no alcohólico (HGNA), siendo ésta la primera causa de trasplante hepático en Chile en población adulta. Se ha observado que las personas con síndrome de Gilbert, caracterizado por mutaciones en UGT1A1 y niveles séricos de bilirrubina ligeramente elevados, podría mostrar una menor incidencia de hígado graso, en relación con personas con niveles de bilirrubina normales. Objetivo: Evaluar la asociación entre bilirrubina sérica y presencia de hígado graso no alcohólico en participantes del estudio chileno de crecimiento y obesidad (ECO), con un enfoque de randomización mendeliana usando genotipos UGT1A1 como variable instrumental. Metodología: Se analizaron 750 adolescentes participantes de la cohorte chilena ECO, con edad promedio de 15.4 ± 0.98 años, 51.6% mujeres. Un 9.6% de la muestra presenta diagnóstico de hígado graso evaluado mediante ultrasonografía. Además, se cuenta con mediciones antropométricas (IMC, presión arterial) y metabólicas (pruebas hepáticas). Se determinaron niveles séricos de bilirrubina total y directa. El genotipo UGT1A1 (rs6742078) se determinó mediante uso selectivo de información procedente del microarreglo genómico MEGA-Illumina. La asociación entre variables se evaluó mediante regresión lineal y regresión logística múltiple. Resultados: La asociación entre bilirrubina plasmática total e hígado graso resultó en una odds ratio significativo de 0.70 (IC 95%; 0.51 – 0.97; p=0.03). Sin embargo, la asociación entre genotipos rs6742078 de UGT1A1 e hígado graso resultó en una odds ratio no significativa de 1.41 para el genotipo GT (IC 95%: 0.77 – 2.59; P = 0.27) y 0.80 para el genotipo TT (IC 95%: 0.29 – 2.18; P = 0.66) (referencia: genotipo GG), tras ajuste por edad, sexo, índice de masa corporal y tres componentes principales de etnia. Conclusión: Existe una asociación significativa entre niveles de bilirrubina plasmáticos y presencia de hígado graso en adolescentes. Sin embargo, al análisis de randomización mendeliana con genotipos UGT1A1 no ha podido demostrar inequívocamente que esta asociación sea de tipo causal.
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    Circulating Bilirubin Levels, but Not Their Genetic Determinants, Are Inversely Associated with Steatotic Liver Disease in Adolescents
    (2025) Miranda Marin, Jose Patricio; Gana, Juan Carlos; Alberti, Gigliola; Galindo Muñoz, Karen Melissa; Pereira, Ana; Santos Martín, José Luis
    Epidemiologic studies suggest that elevated plasma unconjugated bilirubin confer protection against steatotic liver disease (SLD) in adults. However, evidence supporting this protective role in adolescents remains limited. We aimed to assess the association between serum bilirubin levels and their genetic determinants in protecting against SLD in Chilean adolescents. We conducted a cross-sectional study with 704 adolescents aged 15.4 ± 1 years (52% girls) of the Chilean Growth and Obesity Cohort Study. Ultrasonography echogenicity was used to diagnose SLD. We measured Z-scores of body mass index (z-BMI), total bilirubin (TB), and the genetic determinants of bilirubin (including rs887829 genotypes of UGT1A1 and bilirubin polygenic scores). Multiple logistic regression models evaluated the associations between standardized TB and its genetic determinants with SLD. We found that 1-SD of standardized plasma TB was significantly associated with a 30% reduction in the likelihood of SLD after adjustment by sex, age, z-BMI, and ethnicity (OR = 0.7; 95% CI = 0.50–0.96; p = 0.03). No significant associations were found among the rs887829 genotypes, bilirubin polygenic scores, and SLD in logistic regression models adjusted by covariates. Increased circulating bilirubin levels are unlikely causally associated with protection against SLD, and the cross-sectional association could be due to unmeasured confounding.
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    Circulating Bilirubin Levels, but Not Their Genetic Determinants, Are Inversely Associated with Steatotic Liver Disease in Adolescents
    (2025) Miranda Marin, Jose Patricio; Gana, Juan Carlos; Alberti, Gigliola; Galindo Muñoz, Karen Melissa; Pereira, Ana; Santos Martín, José Luis
    Epidemiologic studies suggest that elevated plasma unconjugated bilirubin confer protection against steatotic liver disease (SLD) in adults. However, evidence supporting this protective role in adolescents remains limited. We aimed to assess the association between serum bilirubin levels and their genetic determinants in protecting against SLD in Chilean adolescents. We conducted a cross-sectional study with 704 adolescents aged 15.4 ± 1 years (52% girls) of the Chilean Growth and Obesity Cohort Study. Ultrasonography echogenicity was used to diagnose SLD. We measured Z-scores of body mass index (z-BMI), total bilirubin (TB), and the genetic determinants of bilirubin (including rs887829 genotypes of UGT1A1 and bilirubin polygenic scores). Multiple logistic regression models evaluated the associations between standardized TB and its genetic determinants with SLD. We found that 1-SD of standardized plasma TB was significantly associated with a 30% reduction in the likelihood of SLD after adjustment by sex, age, z-BMI, and ethnicity (OR = 0.7; 95% CI = 0.50–0.96; p = 0.03). No significant associations were found among the rs887829 genotypes, bilirubin polygenic scores, and SLD in logistic regression models adjusted by covariates. Increased circulating bilirubin levels are unlikely causally associated with protection against SLD, and the cross-sectional association could be due to unmeasured confounding.