Role of C/A Polymorphism at 220 on the Expression of

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 220 located between the TATA box and transcriptional initiation site. We show here that when nucleoside A is present at 220, 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 220 is increased on cotransfection of an expression vector containing human estrogen receptor-a 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 220. We also show that reporter constructs containing human angiotensinogen gene promoter with nucleoside C at 220 have increased basal promoter activity on transient transfection in HepG2 cells as compared with reporter constructs with nucleoside A at 220. Our data suggest that C/A polymorphism at 220 may modulate the expression of human angiotensinogen gene in a sex-specific manner. (Hypertension. 1999;33:108-115.) Key Words: angiotensinogen n genes n polymorphism n estrogen n gene regulation n regulation, hormonal n major late transcription factor The renin-angiotensin system plays an important role inthe regulation of blood pressure, fluid balance, and electrolyte homeostasis. Angiotensin II, which is 1 of th