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

Shaked, Abraham; Loza, Bao‐Li; Loon, Elisabet Van; Olthoff, Kim M.; Guan, Weihua; Jacobson, Pamala A.; Fishman, Claire E.; Gao, Hui; Oetting, William S.; Israni, Ajay K.; Testa, Giuliano; Trotter, James F.; Klintmalm, Göran B.; Naesens, Maarten; Asrani, Sumeet K.; Keating, Brendan J.

doi:10.1038/s41591-022-01758-7

Cited by 22 publications

(21 citation statements)

References 65 publications

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“…Recent data have shown that post-liver transplant diabetes can be predicted by polygenic risk scores obtained in the donor and in the recipient. Since metabolic dysfunction involving the glucose metabolic pathway is part of the pathogenesis of NAFLD, 9 the recipient's and the donor's genetic background would likely play a role. Gene expression studies in the explanted livers are clearly of future interest.…”

Section: Discussionmentioning

confidence: 99%

Regression of Graft Steatosis After Liver Transplantation

Meyer,

Maurer,

Staufer

et al. 2022

Prog Transpl

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Introduction: Liver grafts with limited steatosis are currently used for liver transplantation, but the natural history of graft steatosis is not well known. Project Aims or Questions: This program evaluation aimed at assessing changes of steatosis after liver transplantation. Design: A retrospective chart review was performed assessing presence and severity of steatosis in the liver explant and in time zero donor graft biopsies carried out at the time-point of liver transplantation on histopathology and on imaging one year thereafter in 30 well characterized patients. Results: Ten patients (33%) showed steatosis on explant. Time zero biopsy revealed steatosis in 18 grafts (60%) and no steatosis in 12 (40%). One year after transplantation, 8 patients (27%) had steatosis and 22 patients (63%) had none. Fourteen patients (47%) showed changes in steatosis: 12 showed resolution and 2 showed de novo steatosis. Explant macrovesicular steatosis was associated with presence of steatosis 1 year after transplantation (binary logistic regression model, p = 0.014), but not macrovesicular steatosis in the donor graft at time-point of transplantation. Conclusion: Resolution of graft steatosis was frequent. Presence of steatosis in the recipient's liver, but not graft steatosis, was a risk factor for steatosis 1 year after transplantation. Factors related to the recipient seem to prevail over donor-related factors in determining the persistence or de novo appearance of steatosis after liver transplantation.

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Section: Discussionmentioning

confidence: 99%

Regression of Graft Steatosis After Liver Transplantation

Meyer,

Maurer,

Staufer

et al. 2022

Prog Transpl

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“…Each type of molecule only provides a portion of the whole molecular picture, a piece of a complex puzzle [13]. As a consequence, a single component of the transplant-ome often only modestly improves our ability to predict a postoperative complication [14 ▪▪ ]. Understanding how each component of the transplant-omic profile interacts with the others provides a higher resolution view of the molecular state, its causal structure, and clinically actionable targets [13].…”

Section: Disentangling Transplant-omics With Network Biologymentioning

confidence: 99%

Improving liver transplant outcomes with transplant-omics and network biology

Scarpa

2023

Current Opinion in Organ Transplantation

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Purpose of review Molecular omics data is increasingly ubiquitous throughout medicine. In organ transplantation, recent large-scale research efforts are generating the ‘transplant-ome’ – the entire set of molecular omics data, including the genome, transcriptome, proteome, and metabolome. Importantly, early studies in anesthesiology have demonstrated how perioperative interventions alter molecular profiles in various patient populations. The next step for anesthesiologists and intensivists will be to tailor perioperative care to the transplant-ome of individual liver transplant patients. Recent findings In liver transplant patients, elements of the transplant-ome predict complications and point to novel interventions. Importantly, molecular profiles of both the donor organ and recipient contribute to this risk, and interventions like normothermic machine perfusion influence these profiles. As we can now measure various omics molecules simultaneously, we can begin to understand how these molecules interact to form molecular networks and emerging technologies offer noninvasive and continuous ways to measure these networks throughout the perioperative period. Molecules that regulate these networks are likely mediators of complications and actionable clinical targets throughout the perioperative period. Summary The transplant-ome can be used to tailor perioperative care to the individual liver transplant patient. Monitoring molecular networks continuously and noninvasively would provide new opportunities to optimize perioperative management.

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“…In our recent manuscript published in Nature Medicine, 7 we aimed to determine whether well‐established type‐2 diabetes–associated PRS (T2D‐PRS) 8 can stratify the risk exposure for developing T2D within 6–12 months after liver or kidney transplantation and whether the transplanted organs transfer donor genetic risk that would modify recipients’ risk for developing post‐transplant diabetes mellitus (PTDM). The study included liver ( n = 1146) and kidney ( n = 533) transplant recipients for whom both recipients’ and their paired donors’ DNA were available, and for whom we had appropriate pre‐ and post‐transplant medical records which allowed the confirmation of the new onset of T2D.…”

Section: Type‐2 Diabetes Prs Predict the Rapid Onset Of Early Post‐tr...mentioning

confidence: 99%