Aldegheri Luana, Cipullo Chiara, Rosso Natalia, Catamo Eulalia, Casagranda Biagio, Giraudi Pablo, de Manzini Nicolò, Palmisano Silvia, Robino Antonietta
Institute for Maternal and Child Health-IRCCS Burlo Garofolo, 34137 Trieste, Italy.
Metabolic Liver Disease Unit, Fondazione Italiana Fegato-ONLUS, Area Science Park, Basovizza, 34149 Trieste, Italy.
Int J Mol Sci. 2025 Jul 29;26(15):7337. doi: 10.3390/ijms26157337.
Metabolic and bariatric surgery (MBS) is an effective treatment for severe obesity, though individual responses vary widely, partly due to genetic predisposition. This study investigates the association of a body mass index (BMI) polygenic score (PGS) with weight loss and metabolic outcomes following surgery. A cohort of 225 patients undergoing MBS was analyzed at baseline (T), six (T), and twelve (T) months, with anthropometric and biochemical parameters recorded at each time point. Total weight loss (TWL) and excess weight loss (EWL) percentages were calculated. PGS was computed using the LDpred-grid Bayesian method. The mean age was 45.9 ± 9.4 years. Males had a higher baseline prevalence of type 2 diabetes (T2D) and comorbidities ( < 0.001). Linear regression analysis confirmed an association between PGS and baseline BMI ( = 0.012). Moreover, mediation analysis revealed that baseline BMI mediated the effect of the PGS on %TWL at T, with an indirect effect (-value = 0.018). In contrast, high-density lipoprotein-cholesterol (HDL-C) at T and triglycerides (TG) at T showed direct associations with the PGS (-value = 0.004 and -value = 0.08, respectively), with no significant mediation by BMI. This study showed a BMI-mediated association of PGS with %TWL and a direct association with lipid changes, suggesting its potential integration into personalized obesity treatment.
代谢与减重手术（MBS）是治疗重度肥胖的有效方法，尽管个体反应差异很大，部分原因是遗传易感性。本研究调查了体重指数（BMI）多基因评分（PGS）与手术后体重减轻和代谢结果之间的关联。对225例接受MBS的患者队列在基线（T0）、6个月（T6）和12个月（T12）时进行分析，在每个时间点记录人体测量和生化参数。计算总体重减轻（TWL）和超重减轻（EWL）百分比。使用LDpred-grid贝叶斯方法计算PGS。平均年龄为45.9±9.4岁。男性2型糖尿病（T2D）和合并症的基线患病率更高（P<0.001）。线性回归分析证实PGS与基线BMI之间存在关联（P = 0.012）。此外，中介分析显示基线BMI介导了PGS对T0时TWL百分比的影响，间接效应显著（P值 = 0.018）。相比之下，T0时的高密度脂蛋白胆固醇（HDL-C）和T12时的甘油三酯（TG）与PGS呈直接关联（P值分别为0.004和0.08），BMI无显著中介作用。本研究表明PGS与TWL百分比之间存在BMI介导的关联，与脂质变化存在直接关联，表明其有可能整合到个性化肥胖治疗中。
