Biopharmaceutics and Biologic Drugs

Background: Hypertension is one of the major risk factors for cardiovascular diseases. It has been suggested that genetic backgrounds, which have an association with essential hypertension, may also determine the responsiveness to ACE inhibitor. We determined the association of angiotensinogen gene polymorphism with essential hypertension and the relationship between polymorphism in the angiotensinogen (M235T) gene and blood pressure response to ACE inhibitor (enalapril) in patients with essential hypertension. Th e present study is also about a particular genetic polymorphism (A1166C), gene expression and protein expression of the angiotensin II type I receptor (AT1R) and its association with essential hypertension in a Northern Indian population. Methods: 250 patients with essential hypertension and 250 normal healthy controls from Delhi and surrounding areas were recruited for the investigation. Blood pressure was recorded before and aft er 6 weeks of treatment with ACE inhibitors, Enalapril. Genotyping were carried out by PCR and RFLP technique and expression analysis at mRNA levels by real-time PCR. Results and Conclusions: Statistically signifi cant association of T allele was observed with essential hypertension [x2=14.67, p=0.00013, Odds ratio=1.76 (1.3-2.32) at 95% CI]. Th e decrease in systolic blood pressure and diastolic blood pressure after six weeks of treatment of the patients carrying TT genotype were greater than the groups carrying MT and MM genotypes. Th e angiotensinogen (M235T) gene polymorphism is signifi cantly associated with essential hypertension. Patients carrying TT genotype had higher blood pressure lowering response when treated with ACE inhibitor, Enalapril than those carrying MM and MT genotypes suggesting that the T allele may be a possible genetic marker for essential hypertension. Our findings also suggest that C allele of A1166C polymorphism in the angiotensin II type 1 receptor gene is associated with essential

hypertension and its upregulation could play an important role in essential hypertension