YIA 03-05 BLOOD PRESSURE REDUCTION AND DIFFERENT C/EBPα-DNA BINDING PATTERN IN TELMISARTAN-TREATED ANGIOTENSINOGEN G-217A POLYMORPHISM HYPERTENSIVE PATIENTS.

OBJECTIVE: To investigate whether the angiotensinogen (AGT) G-217A polymorphism affects blood pressure response of telmisartan and valsartan in hypertensive patients.

DESIGN AND METHOD: A total of 46 primary hypertensive patients, 23 patients received telmisartan 80 mg and 23 patients received valsartan 160 mg, were observed and followed up for 4 months. The AGT G-217A polymorphism was determined by PCR-RFLP and direct sequencing method. Blood pressure response was measured daytime (6 am - 10 pm), night-time (10 pm - 6 am), and 24 hours using twenty-four hours ambulatory blood pressure monitoring (ABPM). Plasma AGT level were performed at baseline and after 4 months of ARB therapy. The docking procedure between C/EBPα (1NWQ) and oligonucleotides containing -217G and -217A was analyzed by patchdock and firedock. The visualization of the structures were done by PyMol.

RESULTS: Significantly reduced blood pressure in both daytime and 24 hours mean systolic/diastolic blood pressure were observed in patients with -217AA/AG genotype who received telmisartan, but not valsartan, compared to those carrying GG genotype. In line with the change of blood pressure, the change of plasma AGT level in those carrying -217AA/AG were slightly lower compared to GG genotype in telmisartan-treated group, even it failed to reach stastistically significant (p = 0.17). We suggested the variability antihypertensive response in telmisartan-treated AGT G-217A polymorphism hypertensive patients might correlate with the change in AGT expression due to the PPARγ-activating property of telmisartan, that involved C/EBPα. The adenine at position -217 formed a favoured hydrogen bond with Asn which is important for stabilizing the C/EBPα - DNA interface. This likely influences C/EBPα activity to repress AGT expression in response to PPARγ-activated telmisartan.

CONCLUSIONS: AGT G-217A polymorphism may increases the antihypertensive response of telmisartan by forming a favoured hydrogen bond with Asn of C/EBPα protein.