Role of C/A Polymorphism at −20 on the Expression of Human Angiotensinogen Gene

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Abstract
—Angiotensinogen is the glycoprotein precursor of 1 of the most potent vasoactive hormones, angiotensin II. Human angiotensinogen gene contains a C/A polymorphism at −20 located between the TATA box and transcriptional initiation site. We show here that when nucleoside A is present at −20, this sequence binds to the estrogen receptor. We also show that transcriptional activity of reporter constructs containing human angiotensinogen gene promoter with nucleoside A at −20 is increased on cotransfection of an expression vector containing human estrogen receptor-α coding sequence in human hepatoma cells (HepG2) followed by estrogen treatment. On the other hand, adenoviral major late transcription factor binds preferentially to this region of the promoter when nucleoside C is present at −20. We also show that reporter constructs containing human angiotensinogen gene promoter with nucleoside C at −20 have increased basal promoter activity on transient transfection in HepG2 cells as compared with reporter constructs with nucleoside A at −20. Our data suggest that C/A polymorphism at −20 may modulate the expression of human angiotensinogen gene in a sex-specific manner.