Pharmacogenomics of Antihypertensive Drugs in Brazil: Recent Progress and Clinical Implications

Abstract

Background: The available antihypertensive drugs are effective and well tolerated agents. However, only about half of patients with treated hypertension achieve appropriate blood pressure control. Genetic and non-genetic factors contribute to the interindividual variability of the therapeutic response Objective: This review constitutes a comprehensive update of the pharmacogenomics of antihypertensive drugs and their clinical implications in Brazil. Results: Twenty-five studies explored the influence of gene variants on drug response in patients with primary, resistant, or gestational hypertension. Variants in BDKRB2, NOS3, PRKCA, and VEGFA influenced the response to enalapril in patients with primary hypertension. AGT and MMP2 variants were associated with high risk of resistance to antihypertensive treatment, whereas NOS2 variants were related to low risk. Moreover, NAT2 slow acetylators showed an increased response to hydralazine in patients with resistant hypertension. HMOX1, NAMPT, MMP9, NOS3 and TIMP1 variants might be markers of drug responsiveness in hypertensive or preeclamptic pregnant women. Power and replication of studies, polygenic nature of response to therapy, and treatment with multiple drugs were important challenges to be overcome for identifying genetic predictors of antihypertensive response in Brazil. Conclusion: Pharmacogenomic studies in Brazilian cohorts provide some evidences of variants, mainly in pharmacodynamics genes, which influence the response to antihypertensive drugs. However, some findings are limited by cohort size or therapeutic scheme and may be influenced by interactions with other genetic and non-genetic factors. Therefore, further investigations are needed to elucidate the contribution of pharmacogenomics to the efficacy and safety of antihypertensive therapy.