PMID- 31303410
OWN - NLM
STAT- MEDLINE
DCOM- 20191125
LR  - 20211204
IS  - 1873-2623 (Electronic)
IS  - 0041-1345 (Linking)
VI  - 51
IP  - 6
DP  - 2019 Jul-Aug
TI  - SNPs Within the MTOR Gene Are Associated With an Increased Risk of Developing De 
      Novo Diabetes Mellitus Following the Administration of Everolimus in Liver 
      Transplant Recipients.
PG  - 1962-1971
LID - S0041-1345(18)31326-5 [pii]
LID - 10.1016/j.transproceed.2019.03.027 [doi]
AB  - BACKGROUND: The impact of immunosuppressive drugs in patients following liver 
      transplantation (LT) is very individual. Despite the multiple beneficial effects 
      of the mammalian target of rapamycin (mTOR) inhibitor everolimus (EVR) in LT 
      recipients, some patients do not benefit from EVR administration. We investigated 
      whether the presence of common single-nucleotide polymorphisms (SNPs) in the mTOR 
      gene are predictive for adverse events following the introduction of EVR after 
      LT. MATERIALS AND METHODS: The feasibility and efficacy of EVR in 127 liver 
      transplant recipients who were converted to EVR-based immunosuppression was 
      documented retrospectively. Blood samples of these patients were analyzed for the 
      occurrence of 4 SNPs in the mTOR promoter region (mTOR3099/rs2295079 C>G, 
      mTOR3162/rs2295080 A>C) and the mTOR 3' untranslated regio (mTOR8167/rs12139042 
      C>T, mTOR8600/rs2536 A>G); the specific allele variants were also associated with 
      the incidence of adverse events (AEs). RESULTS: Of all patients, 21 (16.5%) did 
      not tolerate the medication and had to discontinue. Of those patients who 
      continued, 37% developed signs of reduced tolerance within the first 6 months, 
      resolving after 12 months. When the cohort was divided according to genotype and 
      allele frequency, patients with the mTOR3162/rs2295080 CC variant had a 
      significantly higher risk (odds ratio = 5.89; 95% confidence interval = 
      1.48-23.40; P = .012) of developing new-onset diabetes mellitus following EVR 
      treatment than AA or AC genotype carriers. CONCLUSION: Our results suggest that 
      the SNP mTOR3162/rs2295080 CC genotype is associated with the development of 
      new-onset diabetes mellitus following EVR treatment.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Husen, Peri
AU  - Husen P
AD  - Department of General, Visceral- and Transplantation Surgery, Faculty of 
      Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, 
      Germany.
FAU - Straub, Katja
AU  - Straub K
AD  - Department of Gastroenterology and Hepatology, Faculty of Medicine, University 
      Hospital Essen, University of Duisburg-Essen, Essen, Germany.
FAU - Willuweit, Katharina
AU  - Willuweit K
AD  - Department of Gastroenterology and Hepatology, Faculty of Medicine, University 
      Hospital Essen, University of Duisburg-Essen, Essen, Germany.
FAU - Hagemann, Anna
AU  - Hagemann A
AD  - Institute of Pharmacology and Toxicology, School of Medicine, Faculty of Health, 
      Witten/Herdecke University, Witten, Germany.
FAU - Wedemeyer, Heiner
AU  - Wedemeyer H
AD  - Department of Gastroenterology and Hepatology, Faculty of Medicine, University 
      Hospital Essen, University of Duisburg-Essen, Essen, Germany.
FAU - Bachmann, Hagen S
AU  - Bachmann HS
AD  - Institute of Pharmacology and Toxicology, School of Medicine, Faculty of Health, 
      Witten/Herdecke University, Witten, Germany; Institute of Pharmacogenetics, 
      Faculty of Medicine, University Hospital Essen, University of Duisburg-Essen, 
      Essen, Germany.
FAU - Herzer, Kerstin
AU  - Herzer K
AD  - Department of Gastroenterology and Hepatology, Faculty of Medicine, University 
      Hospital Essen, University of Duisburg-Essen, Essen, Germany. Electronic address: 
      kerstin.herzer@uk-essen.de.
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
DEP - 20190711
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Diabetes Mellitus/*chemically induced/genetics
MH  - Everolimus/*adverse effects
MH  - Female
MH  - Humans
MH  - Immunosuppression Therapy/adverse effects/methods
MH  - Immunosuppressive Agents/*adverse effects
MH  - Liver Transplantation/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Postoperative Complications/*chemically induced/genetics
MH  - Retrospective Studies
MH  - TOR Serine-Threonine Kinases/*genetics
EDAT- 2019/07/16 06:00
MHDA- 2019/11/26 06:00
CRDT- 2019/07/16 06:00
PHST- 2018/10/15 00:00 [received]
PHST- 2019/02/27 00:00 [revised]
PHST- 2019/03/13 00:00 [accepted]
PHST- 2019/07/16 06:00 [pubmed]
PHST- 2019/11/26 06:00 [medline]
PHST- 2019/07/16 06:00 [entrez]
AID - S0041-1345(18)31326-5 [pii]
AID - 10.1016/j.transproceed.2019.03.027 [doi]
PST - ppublish
SO  - Transplant Proc. 2019 Jul-Aug;51(6):1962-1971. doi: 
      10.1016/j.transproceed.2019.03.027. Epub 2019 Jul 11.