The TCF7L2 T-allele alters triglyceride response and may reduce the risk of developing cardiovascular disease
A new article published in Scientific Reports (February 2017) by Danish Diabetes Academy PhD student Line Engelbrechtsen, University of Copenhagen, shows that carriers of the type 2 diabetes susceptibility gene variant, the TCF7L2 rs790346 T-allele, have altered postprandial triglyceride response, which may suggest a link between TCF7L2 and hepatic lipid regulation.
TCF7L2 GENE VARIANTS INCREASE THE RISK OF TYPE 2 DIABETES
Variants within the transcription factor 7-like 2 gene (TCF7L2) are the strongest common genetic risk factors associated with development of type 2 diabetes (T2D). Several variants within this gene have been shown to increase the risk of diabetes by 30–50%; in which the rs7903146 has the largest and most consistent effect on diabetes susceptibility. Carriers of TCF7L2 risk variants have alterations in their glucose metabolism leading to decreased insulin production, β –cell dysfunction and altered hepatic gluconeogenesis. The biological mechanism mediating these alterations is largely unknown. Therefore, we aimed to identify alterations in circulating metabolites among carriers, in order to identify a possible effect on metabolism, which arises prior to glucose intolerance and diabetes.
CARRIERS OF THE HIGH RISK T-ALLELE HAVE ALTERED TRIGLYCERIDE RESPONSE
In this study, we used a NMR metabolomics platform which allows characterization of selected circulating metabolites among study participants. We investigated the metabolite response following a meal test among 31 homozygous high-risk T-allele carriers and 31 homozygous low-risk C-allele carriers. Our results show that the rate of change(concentration/min) of several subclasses of lipid particles are lower in high risk T- allele carriers during a meal test, with a strong effect on triglyceride levels, mainly influencing high-density lipoprotein (HDL) and very low density lipoprotein (VLDL) subclasses.
Our study suggest that T-allele carriers have altered lipid metabolism, possibly mediating a protective effect against elevated triglycerides and triglyceride-rich particles, which may translate in to a decrease in risk of developing atherosclerosis.
AUTHORS AND AFFILIATIONS
L. Engelbrechtsen1,2, T. H. Hansen1, Y. Mahendran1,2 P. Pyl1, E. Andersson1, A. Jonsson1, A. Gjesing1, A. Linneberg3,4,5, T. Jørgensen3,6,7, T. Hansen1 & H. Vestergaard1,8
1Section of Metabolic Genetics, Novo Nordisk Research Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 1, DIKU-building 1. Floor, DK-2100 Copenhagen
2Danish Diabetes Academy, Odense, Denmark
3Research Centre for Prevention and Health, The Capital Region of Denmark, Denmark
4Department of Clinical Experimental Research, Rigshospitalet, Denmark
5Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
6Department of Public health, Faculty of Health Science, University of Copenhagen, Denmark
7Faculty of Medicine, Aalborg University, Denmark
8Steno Diabetes Center, Gentofte, Denmark
Source: Scientific Reports