Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• The pharmacogenomics journal, 2017-01, Vol.17 (1), p.69-75

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 =197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n =1294 and n =759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n =46'186, n =123'865, n >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 <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.