载有 TCF7L2-rs7903146 风险基因型的个体血清素水平升高。

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

机构信息

Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.

Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.

出版信息

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

DOI:10.1038/s41598-019-49347-y

PMID:31492908

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6731216/

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 (n = 154) and a validation (n = 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.

摘要

转录因子 7 样 2（TCF7L2）多态性 rs7903146 已知与 2 型糖尿病的风险升高密切相关，但其分子机制仍不清楚。我们使用靶向代谢组学方法，在一项发现（n=154）和验证（n=240）研究中，评估了总共 394 名患者血清样本的代谢谱，以了解其 rs7903146 基因型。我们发现，携带风险等位基因的个体中，血清素是增加最多的代谢物。在包括 2 型糖尿病在内的全调整后，以及在进一步排名靠前的代谢物后，血清素与 rs7903146 基因型显著相关。鉴于外周血清素在代谢稳态和 2 型糖尿病中的作用，这一发现首次提示，TCF7L2 多态性对 2 型糖尿病风险的显著影响可能涉及到一种依赖于血清素的途径。