美国宾夕法尼亚大学Abraham Shaked等研究人员发现，捐赠者和接受者的多基因风险评分影响移植后糖尿病的风险。相关论文于2022年4月7日在线发表在《自然—医学》杂志上。

研究人员表示，移植后糖尿病（PTDM）降低了异体移植和受体的寿命。多基因风险评分（PRS）显示出与2型糖尿病（T2D）的更大风险有密切关系。

研究人员报道了肝脏受体（n=1,581）及其供体（n=1,555）以及肾脏受体（n=2,062）及其供体（n=533）的PTDM与T2D PRS的关系。受体T2D PRS与移植前T2D和PTDM的发展有关。肝脏捐赠者的T2D PRS，但不是肾脏捐赠者，是PTDM发展的独立风险因素。与仅包括临床特征的模型相比，将肝脏供体和受体T2D PRS结合起来，可明显提高PTDM的预测率：结合T2D PRS的曲线下面积（AUC）为67.6%（95%置信区间（CI）64.1-71.1%），而临床特征模型为62.3%（95%CI 58.8-65.8%）（P=0.0001）。在合并捐赠者和接受者T2D PRS的最高五分位数的肝脏接受者具有最大的PTDM风险，与最低五分位数的人相比，比值比为3.22（95% CI 2.07-5.00）（P=1.92 × 10^-7）。

总之，T2D PRS可识别出具有高风险PTDM的移植候选人，可能需要对其进行预先的糖尿病管理和供体选择。

附：英文原文

Title: Donor and recipient polygenic risk scores influence the risk of post-transplant diabetes

Author: Shaked, Abraham, Loza, Bao-Li, Van Loon, Elisabet, Olthoff, Kim M., Guan, Weihua, Jacobson, Pamala A., Zhu, Andrew, Fishman, Claire E., Gao, Hui, Oetting, William S., Israni, Ajay K., Testa, Giuliano, Trotter, James, Klintmalm, Goran, Naesens, Maarten, Asrani, Sumeet K., Keating, Brendan J.

Issue&Volume: 2022-04-07

Abstract: Post-transplant diabetes mellitus (PTDM) reduces allograft and recipient life span. Polygenic risk scores (PRSs) show robust association with greater risk of developing type2 diabetes (T2D). We examined the association of PTDM with T2D PRS in liver recipients (n=1,581) and their donors (n=1,555), and kidney recipients (n=2,062) and their donors (n=533). Recipient T2D PRS was associated with pre-transplant T2D and the development of PTDM. T2D PRS in liver donors, but not in kidney donors, was an independent risk factor for PTDM development. The inclusion of a combined liver donor and recipient T2D PRS significantly improved PTDM prediction compared with a model that included only clinical characteristics: the area under the curve (AUC) was 67.6% (95% confidence interval (CI) 64.1–71.1%) for the combined T2D PRS versus 62.3% (95% CI 58.8–65.8%) for the clinical characteristics model (P=0.0001). Liver recipients in the highest quintile of combined donor and recipient T2D PRS had the greatest risk of PTDM, with an odds ratio of 3.22 (95% CI 2.07–5.00) (P=1.92×107) compared with those in the lowest quintile. In conclusion, T2D PRS identifies transplant candidates with high risk of PTDM for which pre-emptive diabetes management and donor selection may be warranted.

DOI: 10.1038/s41591-022-01758-7

Source: https://www.nature.com/articles/s41591-022-01758-7