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

Publication

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

Journal Paper/Review - Dec 8, 2015

Quteineh L, Eap C B, Pascual M, Soccal P M, Dufour J-F, Mohacsi P, Steiger J, van Delden C, Binet Françoise-Isabelle, Mueller N J, Lehmann R, Treyer A, Kutalik Z, Manuel O, Venetz J-P, Crettol S, Golshayan D, Bochud P-Y, and The Swiss Transplant Cohort Study

Citation

Quteineh L, Eap C, Pascual M, Soccal P, Dufour J, Mohacsi P, Steiger J, van Delden C, Binet F, Mueller N, Lehmann R, Treyer A, Kutalik Z, Manuel O, Venetz J, Crettol S, Golshayan D, Bochud P, and The Swiss Transplant Cohort Study. CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation. Pharmacogenomics J 2015; 17:69-75.

Type

Journal Paper/Review (English)

Journal

Pharmacogenomics J 2015; 17

Publication Date

Dec 8, 2015

Issn Electronic

1473-1150

Pages

69-75

Brief description/objective

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.