title: A Physiologic Approach to the Pharmacogenomics of Hypertension.
abstract: Hypertension is a multifactorial condition with diverse physiological systems contributing to its pathogenesis. Individuals exhibit significant variation in their response to antihypertensive agents. Traditional markers, such as age, gender, diet, plasma renin level, and ethnicity, aid in drug selection. However, this review explores the contribution of genetics to facilitate antihypertensive agent selection and predict treatment efficacy. The findings, reproducibility, and limitations of published studies are examined, with emphasis placed on candidate genetic variants affecting drug metabolism, the renin-angiotensin system, adrenergic signalling, and renal sodium reabsorption. Single-nucleotide polymorphisms identified and replicated in unbiased genome-wide association studies of hypertension treatment are reviewed to illustrate the evolving understanding of the disease's complex and polygenic pathophysiology. Implementation efforts at academic centers seek to overcome barriers to the broad adoption of pharmacogenomics in the treatment of hypertension. The level of evidence required to support the implementation of pharmacogenomics in clinical practice is considered.
authors.affiliation: Division of Nephrology and Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN; and Section of Nephrology, University of Chicago, Chicago, IL.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Eadon
authors.affiliation: Division of Nephrology and Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN; and Section of Nephrology, University of Chicago, Chicago, IL. Electronic address: Achapman1@medicine.bsd.uchicago.edu.
authors.forename: Arlene B
authors.initials: AB
authors.lastname: Chapman
mesh_terms: D000959:Antihypertensive Agents / Q000378:metabolism* / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D012964:Sodium / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D011943:Receptors, Adrenergic, beta; D003577:Cytochrome P-450 Enzyme System; D012964:Sodium
keywords: Antihypertensive; Cytochrome P450; Implementation; Pharmacogenomics