Single nucleotide polymorphisms in the human corticosteroid-binding globulin promoter alter transcriptional activity

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 HNF1.We also found a negative promoter response to dexamethasone-activated glucocorticoid receptor(GR),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.