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

• Published in: The pharmacogenomics journal 2017-01, Vol.17 (1), p.69-75
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 45; 45/77; 631/208/2489; 692/53/2423; Biomedical and Life Sciences; Biomedicine; Body mass index; Body weight; Cholesterol; Cyclic AMP response element-binding protein; Diabetes mellitus; Diabetes Mellitus - epidemiology; Diabetes Mellitus - genetics; Dyslipidemias - epidemiology; Dyslipidemias - genetics; Gene Expression; Gene Frequency; Gene polymorphism; Genetic Predisposition to Disease; Genotype & phenotype; Glucose metabolism; Heterozygote; High density lipoprotein; Homozygote; Human Genetics; Humans; Hyperlipidemia; Incidence; Kidney transplantation; Linear Models; Logistic Models; Metabolic syndrome; Metabolic Syndrome - diagnosis; Metabolic Syndrome - epidemiology; Metabolic Syndrome - genetics; Multivariate Analysis; Obesity; Obesity - epidemiology; Obesity - genetics; Odds Ratio; Oncology; Organ Transplantation - adverse effects; original-article; Overweight; Pharmacotherapy; Phenotype; Polymorphism, Single Nucleotide; Prevalence; Psychopharmacology; Replication; Risk Assessment; Risk Factors; Switzerland - epidemiology; Tacrolimus; Time Factors; Transcription; Transcription Factors - genetics; Transplants & implants; Treatment Outcome
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2015.82

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 ( n 1 =197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n 2 =1294 and n 3 =759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples ( n 4 =46’186, n 5 =123’865, n 6 >100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450 - AA genotype was associated with NODAT, fasting blood glucose and body mass index ( P corrected 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.