POTENTIAL ROLE OF TCF7L2 GENE VARIANTS ON CARDIAC SYMPATHETIC/PARASYMPATHETIC ACTIVITY

Giuseppe Paolisso (1) , Virginia Boccardi (1) , Immacolata Ambrosino (1) , Michela Papa (1) , Daniela Fiore (1) , Maria Rosaria Rizzo (1) , Michelangela Barbieri (1)

1 Geriatric Medicine and Metabolic Diseases

Variants in Transcription Factor 7-like 2 gene (TCF7L2) have been found strongly associated with an increased risk of type 2 diabetes as well as with an impairment of GLP-1 (glucagon like peptide-1) signalling chain. In rats, stimulation of central GLP-1 receptors increases heart rate and activates autonomic regulatory neurons. We aimed to evaluate the potential role of TCF7L2 gene variants on sympathovagal response in relation to changes in plasma insulin and/or GLP-1 concentration following glucose ingestion. Genotyping was performed for rs12255372 and rs7903146 TCF7L2 gene variants in 250 non related healthy volunteers. Consistent with previous reports, both SNPs were in strong linkage disequilibrium (D'=0.87, r2 =0.76). A subset of 167 patients underwent an oral glucose tolerance test while a continuous recording of Heart Rate Variability was performed. At baseline, no difference in fasting plasma insulin, in GLP-1 levels and in LF/HF ratio between the three genotypes were found. Along with glucose ingestion TT subjects had lower INSAUC (insulin area under curve) as well as higher LF/HFAUC (low frequency/high frequency area under curve) values. No difference in GLP-1AUC between TCF7L2 gene variants was found. A multivariate analysis showed that only INSAUC , GLP1AUC and TCF7L2 gene variants were independently associated with LF/HFAUC. In conclusion TT genotype of rs12255372 and rs7903146 TCF7L2 gene variants is associated with lower insulin secretion and higher cardiosympathetic activity. The effect is independent of GLP-1 and insulin plasma concentrations suggesting a potential role of such gene variants in increasing cardiovascular risk via enhanced sympathetic nervous system activity.

Mots clés: Gene Polymorphism; Glucose Metabolism; Cardiac Electrophisiology

Giuseppe Paolisso, Virginia Boccardi, Immacolata Ambrosino, Michela Papa, Daniela Fiore, et al.. POTENTIAL ROLE OF TCF7L2 GENE VARIANTS ON CARDIAC SYMPATHETIC/PARASYMPATHETIC ACTIVITY. European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.117⟩. ⟨hal-00558094⟩