CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation.

Détails

Ressource 1Télécharger: BIB_342B86B6E988.P001.pdf (742.52 [Ko])
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_342B86B6E988
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation.
Périodique
The pharmacogenomics journal
Auteur(s)
Quteineh L., Bochud P.Y., Golshayan D., Crettol S., Venetz J.P., Manuel O., Kutalik Z., Treyer A., Lehmann R., 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)
and The Swiss Transplant Cohort Study
Contributeur(s)
Achermann R., Aubert J.D., Baumann P., Beldi G., Benden C., Berger C., Binet I., Bochud P.Y., Boely E., Bucher H., Bühler L., Carell T., Catana E., Chalandon Y., Geest S., Rougemont O., Dickenmann M., Duchosal M., Fehr T., Ferrari-Lacraz S., Garzoni C., Gasche Y., Soccal P.G., Giostra E., Golshayan D., Good D., Hadaya K., Hess C., Hillinger S., Hirsch H., Hofbauer G., Huynh-Do U., Immer F., Klaghofer R., Koller M., Kuntzen T., Laesser B., Lehmann R., Lovis C., Manuel O., Marti H.P., Martin P.Y., Meylan P., Mohacsi P., Morard I., Morel P., Mueller U., Mueller N., Mueller-McKenna H., Müller T., Müllhaupt B., Nadal D., Nair G., Pascual M., Passweg J., Ziegler C.P., Rick J., Roosnek E., Rosselet A., Rothlin S., Ruschitzka F., Schanz U., Schaub S., Seiler C., Semmo N., Stampf S., Steiger J., Toso C., Tsinalis D., Delden C.V., Venetz J.P., Villard J., Wick M., Wilhelm M., Yerly P.
ISSN
1473-1150 (Electronic)
ISSN-L
1470-269X
Statut éditorial
Publié
Date de publication
01/2017
Peer-reviewed
Oui
Volume
17
Numéro
1
Pages
69-75
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n1=197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n2=1294 and n3=759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n4=46'186, n5=123'865, n6>100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AA genotype was associated with NODAT, fasting blood glucose and body mass index (Pcorrected<0.05). CRTC2 rs8450-AA genotype was associated with NODAT in the second STCS replication sample (odd ratio (OR)=2.01, P=0.04). In the combined STCS replication samples, the effect of rs8450-AA genotype on NODAT was observed in patients having received SOT from a deceased donor and treated with tacrolimus (n=395, OR=2.08, P=0.02) and in non-kidney transplant recipients (OR=2.09, P=0.02). Moreover, rs8450-AA genotype was associated with overweight or obesity (n=1215, OR=1.56, P=0.02), new-onset hyperlipidemia (n=1007, OR=1.76, P=0.007), and lower high-density lipoprotein-cholesterol (n=1214, β=-0.08, P=0.001). In the population-based samples, a proxy of rs8450G>A was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.

Mots-clé
Diabetes Mellitus/epidemiology, Diabetes Mellitus/genetics, Dyslipidemias/epidemiology, Dyslipidemias/genetics, Gene Frequency, Genetic Predisposition to Disease, Heterozygote, Homozygote, Humans, Incidence, Linear Models, Logistic Models, Metabolic Syndrome X/diagnosis, Metabolic Syndrome X/epidemiology, Metabolic Syndrome X/genetics, Multivariate Analysis, Obesity/epidemiology, Obesity/genetics, Odds Ratio, Organ Transplantation/adverse effects, Phenotype, Polymorphism, Single Nucleotide, Prevalence, Risk Assessment, Risk Factors, Switzerland/epidemiology, Time Factors, Transcription Factors/genetics, Treatment Outcome
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/12/2015 9:28
Dernière modification de la notice
20/08/2019 13:20
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