Apport du gène Transcription factor 7-like 2 (TCF7L2) au diabète induit par les statines
Statins usage increases the risk of diabetes apparition by 11% compared to a placebo [1]. In the present study, we used a genomic approach focused on the TCF7L2 gene, strongly linked to diabetes, to show the relationship with statin-induced diabetes. We used data from two Phase 4 randomized clinical trial studies where statins where used: TNT (Treating to New Targets) and IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering). Both studies compare a high atorvastatin dosage (80 mg) to either a moderate dose or a lower dose simvastatin. The genomic study was performed using the MEGA genotyping chip (Illumina). Statistical results of both studies were combined by meta-analysis. Our results show a 16% increase in risk of new onset of diabetes (p=0.022) in high dosage users, compared to lower dosage users confirming our observations. We show that the T allele of the rs7903146 variant of the TCF7L2 gene has a 29% increase in risk of diabetes at baseline or any time during the study (p=1.98E-13) compared to the C allele in any dosage. No genetic variant in or near the TCF7L2 gene was associated to the new onset diabetes in both high and low statins dosage. Furthermore, the rs7903146 variant was not significantly associated with diabetes aggravation in subjects who had diabetes at study baseline (p=0.266). These results contribute to a better understanding of the role of the TCF7L2 gene and the risk of new onset of type 2 diabetes in statins users.
Transcription factor 7-like 2 gene TCF7L2 Treating New Targets TNT Incremental Decrease in End Points Through Aggressive Lipid Lowering IDEAL statin genetic epidemiology type 2 diabetes pharmecogenomics meta-analysis atorvastatin simvastatin