Document Detail


Potential role of TCF7L2 gene variants on cardiac sympathetic/parasympathetic activity.
MedLine Citation:
PMID:  20648057     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Variants in transcription factor 7-like 2 (266096218TCF7L2266096218USuser266096218Gene names have been italicized per house style. Please check and confirm whether there are other instances that need to be italicized or instances where italics have been inappropriately applied.) gene have been found strongly associated with an increased risk of type 2 diabetes, as well as with an impairment of glucagon-like peptide-1 (GLP-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 polymorphisms on sympathovagal response in relation to changes in plasma insulin and/or GLP-1 concentration after glucose ingestion. Genotyping was performed for rs12255372 and rs7903146 TCF7L2 gene variants in 250 non-related healthy volunteers (mean age 27±3 years). Consistent with previous reports, both single-nucleotide polymorphisms were in strong linkage disequilibrium (D'=0.87, r(2)=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 differences in fasting plasma insulin, in GLP-1 levels and in LF/HF (low frequency/high frequency) ratio between the three genotypes were found. Along with glucose ingestion TT subjects had lower INS(AUC) (insulin area under curve), as well as higher LF/HF(AUC) (LF/HF area under curve) values. No difference in GLP-1(AUC) (GLP-1 area under curve) between TCF7L2 gene variants was found. A multivariate analysis including multiple covariates showed that only INS(AUC,) GLP-1(AUC) and TCF7L2 gene variants were independently associated with LF/HF(AUC). In conclusion, TT genotype of rs12255372 and rs7903146 TCF7L2 gene variants is associated with lower insulin secretion and higher cardiosympathetic activity. Moreover, such effect is independent of GLP-1 and insulin plasma concentrations suggesting a potential role of such gene variants in increasing cardiovascular risk through enhanced sympathetic nervous system activity.
Authors:
Virginia Boccardi; Immacolata Ambrosino; Michela Papa; Daniela Fiore; Maria Rosaria Rizzo; Giuseppe Paolisso; Michelangela Barbieri
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Publication Detail:
Type:  Clinical Trial; Journal Article     Date:  2010-07-21
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  18     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-18     Completed Date:  2011-02-28     Revised Date:  2011-12-21    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  1333-8     Citation Subset:  IM    
Affiliation:
Department of Geriatric Medicine and Metabolic Diseases, Second University of Naples, Naples, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Area Under Curve
Blood Glucose / metabolism
Female
Genotype
Glucagon-Like Peptide 1 / blood
Glucose Tolerance Test
Heart / innervation*,  physiology
Humans
Insulin / blood
Linear Models
Male
Parasympathetic Nervous System / metabolism*
Polymorphism, Single Nucleotide / genetics*
Rats
Sympathetic Nervous System / metabolism*
Transcription Factor 7-Like 2 Protein / genetics*
Young Adult
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Insulin; 0/TCF7L2 protein, human; 0/Transcription Factor 7-Like 2 Protein; 89750-14-1/Glucagon-Like Peptide 1

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