Genetic and clinic predictors of new onset diabetes mellitus after transplantation
| Autor: | Christian van Delden, Séverine Crettol, Paola M. Soccal, Isabelle Binet, Nuria Saigi-Morgui, Pierre-Yves Bochud, Paul Mohacsi, Zoltán Kutalik, Manuel Pascual, Nicolas J. Mueller, Jean-François Dufour, Jürg Steiger, Lina Quteineh, Chin B. Eap |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Adolescent Genotype Type 2 diabetes 030226 pharmacology & pharmacy Cohort Studies 03 medical and health sciences Young Adult 0302 clinical medicine Risk Factors Diabetes mellitus Internal medicine Diabetes Mellitus Genetics medicine Humans Prospective Studies Young adult Prospective cohort study Aged Pharmacology ddc:616 ddc:615 Organ Transplantation/adverse effects Receiver operating characteristic Diabetes Mellitus/etiology/genetics business.industry Incidence (epidemiology) Incidence Organ Transplantation Middle Aged medicine.disease Transplantation 030104 developmental biology Molecular Medicine Female business Cohort study |
| Zdroj: | The Pharmacogenomics Journal, Vol. 19, No 1 (2019) pp. 53-64 |
| ISSN: | 1470-269X |
| Popis: | 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 (ORmain: 1.60 [1.36-1.90], p = 3.72*10-8 and ORreplication: 2.14 [1.39-3.41], p = 0.0008, respectively). Two w-GRS were significantly associated with NODAT in the main sample (ORw-GRS 2:1.09 [1.04-1.15], p = 0.001 and ORw-GRS 3:1.14 [1.01-1.29], p = 0.03) and a similar ORw-GRS 2 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. |
| Databáze: | OpenAIRE |
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