Miranda José Patricio, Gana Juan Cristóbal, Alberti Gigliola, Galindo Karen, Pereira Ana, Santos José Luis
Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.
PhD Program in Epidemiology, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.
Int J Mol Sci. 2025 Mar 25;26(7):2980. doi: 10.3390/ijms26072980.
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 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; = 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.
流行病学研究表明，成人血浆中未结合胆红素水平升高可预防脂肪性肝病（SLD）。然而，支持这一保护作用在青少年中的证据仍然有限。我们旨在评估智利青少年血清胆红素水平及其遗传决定因素与预防SLD之间的关联。我们对智利生长与肥胖队列研究中的704名15.4±1岁的青少年（52%为女孩）进行了一项横断面研究。采用超声回声性诊断SLD。我们测量了体重指数Z评分（z-BMI）、总胆红素（TB）以及胆红素的遗传决定因素（包括 和胆红素多基因评分的rs887829基因型）。多元逻辑回归模型评估了标准化TB及其遗传决定因素与SLD之间的关联。我们发现，在按性别、年龄、z-BMI和种族进行调整后，标准化血浆TB每增加1个标准差，SLD发生可能性显著降低30%（比值比=0.7；95%置信区间=0.50-0.96；P=0.03）。在经协变量调整的逻辑回归模型中，未发现rs887829基因型、胆红素多基因评分与SLD之间存在显著关联。循环胆红素水平升高不太可能与预防SLD存在因果关系，这种横断面关联可能是由于未测量的混杂因素所致。
