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YIA 03-05 BLOOD PRESSURE REDUCTION AND DIFFERENT C/EBP&agr;-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/EBP&agr; (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 PPAR&ggr;-activating property of telmisartan, that involved C/EBP&agr;. The adenine at position -217 formed a favoured hydrogen bond with Asn292 which is important for stabilizing the C/EBP&agr; – DNA interface. This likely influences C/EBP&agr; activity to repress AGT expression in response to PPAR&ggr;-activated telmisartan. Conclusions: AGT G-217A polymorphism may increases the antihypertensive response of telmisartan by forming a favoured hydrogen bond with Asn292 of C/EBP&agr; protein.