Association of Angiotensinogen (M235T) Gene Polymorphism with Blood Pressure Lowering Response to Angiotensin Converting Enzyme Inhibitor (Enalapril)

Kamna Srivastava1, Sudhir Chandra1, Jagriti Bhatia2, Rajiv Narang3, Daman Saluja1

1Dr. B.R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, India
2Departments of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
3Departments of Pharmacology and Cardiology, All India Institute of Medical Sciences, New Delhi, India.

Abstract


Purpose: 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 (M235T) 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 from northern Indian subjects. 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 after 6 weeks of treatment with ACE inhibitors, Enalapril. Genotyping were carried out by polymerase chain reaction and Restriction fragment length polymorphism technique. Results: Statistically significant 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], the relative risk at 95% CI being 1.28 (1.2-1.54). The decrease in systolic blood pressure and diastolic blood pressure after six weeks of treatment of the patients carrying TT genotype (SBP = 26±17.4 mmHg, DBP = 14.83±7.6mmHg) were greater than the groups carrying MT (SBP = 3.0±7.8 mmHg, DBP =6.2±3.0 mmHg) and MM genotypes (SBP = 1.2±0.8 mmHg, DBP = 0.10±12.1 mm Hg. Conclusions: The angiotensinogen (M235T) gene polymorphism is significantly 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.

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J Pharm Pharm Sci, 15 (3): 399-406, 2012

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