Dos Santos Quenia, Leung Preston, Thorball Christian W, Ledergerber Bruno, Fellay Jacques, MacPherson Cameron R, Hornum Mads, Terrones-Campos Cynthia, Rasmussen Allan, Gustafsson Finn, Perch Michael, Sørensen Søren S, Ekenberg Christina, Lundgren Jens D, Feldt-Rasmussen Bo, Reekie Joanne
Centre of Excellence for Health, Institut Roche, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Front Mol Biosci. 2023 Dec 7;10:1282412. doi: 10.3389/fmolb.2023.1282412. eCollection 2023.
Type 2 diabetes mellitus (T2DM) can be multifactorial where both genetics and environmental factors play a role. We aimed to investigate the use of polygenic risk scores (PRS) in the prediction of pre-transplant T2DM and post-transplant diabetes mellitus (PTDM) among solid organ transplant (SOT) patients. Using non-genetic risk scores alone; and the combination with PRS, separate logistic regression models were built and compared using receiver operator curves. Patients were assessed pre-transplant and in three post-transplant periods: 0-45, 46-365 and >365 days. A higher PRS was significantly associated with increased odds of pre-transplant T2DM. However, no improvement was observed for pre-transplant T2DM prediction when comparing PRS combined with non-genetic risk scores to using non-genetic risk scores alone. This was also true for predictions of PTDM in all three post-transplant periods. This study demonstrated that polygenic risk was only associated with the risk of T2DM among SOT recipients prior to transplant and not for PTDM. Combining PRS with a clinical model of non-genetic risk scores did not significantly improve the predictive ability, indicating its limited clinical utility in identifying patients at high risk for T2DM before transplantation, suggesting that non-genetic or different genetic factors may contribute to PTDM.
2型糖尿病(T2DM)可能是多因素导致的,遗传因素和环境因素都在其中发挥作用。我们旨在研究多基因风险评分(PRS)在预测实体器官移植(SOT)患者移植前T2DM和移植后糖尿病(PTDM)中的应用。单独使用非遗传风险评分,并将其与PRS相结合,构建了单独的逻辑回归模型,并使用受试者工作特征曲线进行比较。在移植前以及移植后的三个时间段(0 - 45天、46 - 365天和>365天)对患者进行评估。较高的PRS与移植前T2DM的患病几率增加显著相关。然而,将PRS与非遗传风险评分相结合用于预测移植前T2DM时,与单独使用非遗传风险评分相比,并未观察到改善。在所有三个移植后时间段对PTDM的预测中也是如此。这项研究表明,多基因风险仅与SOT受者移植前的T2DM风险相关,而与PTDM无关。将PRS与非遗传风险评分的临床模型相结合并不能显著提高预测能力,这表明其在识别移植前T2DM高风险患者方面的临床效用有限,提示非遗传或不同的遗传因素可能导致PTDM。