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

Article Article scientifique Article CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation eng 2015-12-08 2017 author Quteineh Lina 866410 author Bochud Pierre-Yves 690825 author Golshayan D author Crettol Séverine 593728 author Venetz J-P author Manuel O author Kutalik Z author Treyer Andrea 694011 author Lehmann R author Mueller N J author Binet I author Van Delden Christian 24088 author Steiger J author Mohacsi P author Dufour J-F author Gasche-Soccal Paola Marina Alessandra 33623 author Pascual M author Eap Chin Bin 648560 Swiss Transplant Cohort Study 69-75 10.1038/tpj.2015.82 26644205 1470-269X https://www.nature.com/articles/tpj201582 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. 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 / diagnosis Metabolic Syndrome / epidemiology Metabolic Syndrome / 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 Dewey 615 Dewey 616 Swiss National Science Foundation Etude pharmacogenetique sur les effets secondaires induits par les médicaments psychotropes 144064 CH Projects Roche Organ Transplantation Research Foundation 152358701 Swiss National Science Foundation Deciphering the missing heritability 143914 CH Projects Leenaards Foundation 56 Département de médecine 221 31 Section des sciences pharmaceutiques 17 false 952 Groupe Gasche-Soccal Paola 958 235 Perception du Quorum et gènes de virulence 301 298 Immunologie de transplantation, immunogénétique et thérapie cellulaire 561 Pharmacogenomics journal 17 1 40fe962c-d2fd-4c27-9e8d-a28cb408deb3 Article (Published version) Restricted tpj201582.pdf 192608 application/pdf 17342f5130a5d2e060d05f2eb5d133c1a5d8acaa095e119f91609fde84b6fdb7 8706d8fe-b3da-4c21-9af7-f5226263dda8 Appendix Public 41397_2017_BFtpj201582_MOESM261_ESM.docx 91127 application/vnd.openxmlformats-officedocument.wordprocessingml.document c5aa0b9124b20ce98dd249bbdb728002e9937a1480a2ac2dd02be0d2612bed94 restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté des sciences / Section des sciences pharmaceutiques

Title	Published in	Year	Views	Downloads

CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation	Pharmacogenomics journal	2017	709	0
Pharmacogenetic study on post-transplant diabetes mellitus		2013	193	0

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