Genetic and clinic predictors of new onset diabetes mellitus after transplantation.

Détails

ID Serval
serval:BIB_BA7F0AAB7E2E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Genetic and clinic predictors of new onset diabetes mellitus after transplantation.
Périodique
The pharmacogenomics journal
Auteur(s)
Saigi-Morgui N., Quteineh L., Bochud P.Y., Crettol S., Kutalik Z., Mueller N.J., Binet I., Van Delden C., Steiger J., Mohacsi P., Dufour J.F., Soccal P.M., Pascual M., Eap C.B.
Collaborateur(s)
Swiss Transplant Cohort Study
ISSN
1473-1150 (Electronic)
ISSN-L
1470-269X
Statut éditorial
Publié
Date de publication
02/2019
Peer-reviewed
Oui
Volume
19
Numéro
1
Pages
53-64
Langue
anglais
Résumé
New Onset Diabetes after Transplantation (NODAT) is a frequent complication after solid organ transplantation, with higher incidence during the first year. Several clinical and genetic factors have been described as risk factors of Type 2 Diabetes (T2DM). Additionally, T2DM shares some genetic factors with NODAT. We investigated if three genetic risk scores (w-GRS) and clinical factors were associated with NODAT and how they predicted NODAT development 1 year after transplantation. In both main (n = 725) and replication (n = 156) samples the clinical risk score was significantly associated with NODAT (OR <sub>main</sub> : 1.60 [1.36-1.90], p = 3.72*10 <sup>-8</sup> and OR <sub>replication</sub> : 2.14 [1.39-3.41], p = 0.0008, respectively). Two w-GRS were significantly associated with NODAT in the main sample (OR <sub>w-GRS 2</sub> :1.09 [1.04-1.15], p = 0.001 and OR <sub>w-GRS 3</sub> :1.14 [1.01-1.29], p = 0.03) and a similar OR <sub>w-GRS 2</sub> was found in the replication sample, although it did not reach significance probably due to a power issue. Despite the low OR of w-GRS on NODAT compared to clinical covariates, when integrating w-GRS 2 and w-GRS 3 in the clinical model, the Area under the Receiver Operating Characteristics curve (AUROC), specificity, sensitivity and accuracy were 0.69, 0.71, 0.58 and 0.68, respectively, with significant Likelihood Ratio test discrimination index (p-value 0.0004), performing better in NODAT discrimination than the clinical model alone. Twenty-five patients needed to be genotyped in order to detect one misclassified case that would have developed NODAT 1 year after transplantation if using only clinical covariates. To our knowledge, this is the first study extensively examining genetic risk scores contributing to NODAT development.
Mots-clé
Adolescent, Adult, Aged, Cohort Studies, Diabetes Mellitus/etiology, Diabetes Mellitus/genetics, Female, Genotype, Humans, Incidence, Male, Middle Aged, Organ Transplantation/adverse effects, Prospective Studies, Risk Factors, Young Adult
Pubmed
Web of science
Création de la notice
11/01/2018 9:11
Dernière modification de la notice
04/12/2019 6:30
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