Abstract
Corticosteroid-binding globulin (CBG) is a high-affinity plasma protein that transports glucocorticoids and progesterone. Others and we have reported non-synonymous single nucleotide polymorphisms (SNPs) that influence CBG production or steroid-binding activity. However, no promoter polymorphisms affecting the transcription of human CBG gene (Cbg) have been reported. In the present study we investigated function implications of six promoter SNPs, including −26 C/G, −54 C/T, −144 G/C, −161 A/G, −205 C/A, and −443/−444 AG/−, five of which are located within the first 205 base pairs of 5′-flanking region and close to the highly conserved footprinted elements, TATA-box, or CCAAT-box. Luciferase reporter assays demonstrated that basal activity of the promoter carrying −54 T or −161 G was significantly enhanced. The first three polymorphisms, −26 C/G, −54 C/T, and −144 G/C located close to the putative hepatic nuclear factor (HNF) 1 binding elements, altered the transactivation effect of HNF1β. We also found a negative promoter response to dexamethasone-activated glucocorticoid receptor (GR) α, although none of the SNPs affected its transrepression function. Our results suggest that human Cbg −26 C/G, −54 C/T, −144 G/C, and −161 A/G promoter polymorphisms alter transcriptional activity, and further studies are awaited to explore their association with physiological and pathological conditions.
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Li, Y., Wu, L., Lei, J. et al. Single nucleotide polymorphisms in the human corticosteroid-binding globulin promoter alter transcriptional activity. Sci. China Life Sci. 55, 699–708 (2012). https://doi.org/10.1007/s11427-012-4365-0
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DOI: https://doi.org/10.1007/s11427-012-4365-0