Pharmacogenetic Studies of Antihypertensive Treatment : With Special Reference to the Renin-Angiotensin-Aldosterone System

Abstract: Hypertension is common and constitutes an increased risk of morbidity and mortality of cardiovascular disease. Antihypertensive treatment will reduce this risk; the individual patient's response to treatment, however, is difficult to predict.Patients with hypertension and left ventricular hypertrophy were randomized to monotherapy with either the angiotensin II type 1 receptor antagonist irbesartan or the beta-adrenoreceptor blocker atenolol, and followed for three months. The aim was to determine whether gene polymorphisms in the renin-angiotensin-aldosterone system were related to the response to treatment.The ACE II genotype was associated with the most pronounced diastolic blood pressure response, while the aldosterone synthase (CYP11B2) -344 TT genotype showed the greatest systolic blood pressure response. The angiotensinogen 174 TM genotype showed the most pronounced regression in left ventricular mass, independent of the change in blood pressure. These associations were exhibited only in response to treatment with the angiotensin II type 1 receptor antagonist irbesartan.In a sample of apparently healthy subjects, those with both the D allele and the angiotensinogen 174 TM variant in combination showed a decreased endothelium-dependent vasodilation.These results suggest that the response to antihypertensive treatment is associated with polymorphisms in the genes reflective of the pathophysiological pathway the drug targets. The present study is an encouragement for future investigation, such as large scale studies of multiple polymorphisms and combinations thereof in an attempt to identify a panel of genotypes that can be used as a predictor of an individual patient's response to anithypertensive treatment.