Send to

Choose Destination
FEBS Lett. 2018 Feb;592(3):422-433. doi: 10.1002/1873-3468.12975. Epub 2018 Jan 23.

A candidate functional SNP rs7074440 in TCF7L2 alters gene expression through C-FOS in hepatocytes.

Author information

Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.


The SNP rs7903146 at the transcription factor 7-like 2 (TCF7L2) locus is established as the strongest known genetic marker for type 2 diabetes via genome-wide association studies. However, the functional SNPs regulating TCF7L2 expression remain unclear. Here, we show that the SNP rs7074440 is a candidate functional SNP highly linked with rs7903146. A reporter plasmid with rs7074440 normal allele sequence exhibited 15-fold higher luciferase activity compared with risk allele sequence in hepatocytes, demonstrating a strong enhancer activity at rs7074440. Additionally, we identified C-FOS as an activator binding to the rs7074440 enhancer using a TFEL genome-wide screen method. Consistently, knockdown of C-FOS significantly reduced TCF7L2 expression in hepatocytes. Collectively, a novel enhancer regulating TCF7L2 expression was revealed through searching for functional SNPs.


enhancer; functional SNP; transcription factor; type 2 diabetes

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center