Carriers of a VEGFA enhancer polymorphism selectively binding CHOP/DDIT3 are predisposed to increased circulating levels of thyroid-stimulating hormone

Genetic variants (SNPs) in the vascular endothelial growth factor A (VEGFA) gene are associated with TSH levels. To characterize this association, we searched for SNPs in more than 8000 Danes. We identified rs881858 (in regulatory enhancer region of VEGFA), highly associated with human circulating TSH, which had alleles (A/G) with differential binding to CHOP (C/EBP homology protein) and C/EBPβ (ccaat enhancer binding protein β) proteins.

VEGF is an important angiogenic signal required for tissue expansion and is highly expressed in thyroid tissue. CHOP is a protein induced by cellular stress and these findings suggest a (genetically determined) stress-dependent response in normal or pathophysiological TSH stimulation of the thyroid. (By Dr. Louise Torp Dalgaard, http://jmg.bmj.com/content/early/2016/09/14/jmedgenet-2016-104084 )

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