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Sci Rep. 2019 Sep 6;9(1):12863. doi: 10.1038/s41598-019-49347-y.

Serotonin is elevated in risk-genotype carriers of TCF7L2 - rs7903146.

Author information

1
Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.
2
Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
3
Medical Central Laboratories, Feldkirch, Austria.
4
Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
5
Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria. labor@vivit.at.
6
Private University of the Principality of Liechtenstein, Triesen, Liechtenstein. labor@vivit.at.
7
Drexel University College of Medicine, Philadelphia, PA, USA. labor@vivit.at.
8
Division of Angiology, Swiss Cardiovascular Center, University Hospital of Bern, Bern, Switzerland. labor@vivit.at.

Abstract

The transcription factor 7-like 2 (TCF7L2) polymorphism rs7903146 is known to be tightly associated with an elevated risk for type 2 diabetes, whereas the molecular mechanisms remain elusive. We evaluated the metabolic profile of a total of 394 patients' serum samples with respect to their rs7903146 genotype using targeted metabolomics in a discovery (nā€‰=ā€‰154) and a validation (nā€‰=ā€‰240) study. We have identified serotonin as the top metabolite being increased in carriers of the risk allele. Serotonin was significantly associated with the rs7903146 genotype after full adjustment including type 2 diabetes and further top ranked metabolites. Given the role of peripheral serotonin in metabolic homeostasis and type 2 diabetes, this finding provides a first hint that the well-known impact of the TCF7L2 polymorphism on type 2 diabetes risk may involve a serotonin-dependent pathway.

PMID:
31492908
DOI:
10.1038/s41598-019-49347-y
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