title: G-protein receptor kinase 4 polymorphism and response to antihypertensive therapy.
abstract: BACKGROUND
  G-protein receptor kinase 4 polymorphism influences blood pressure regulation via modulation of dopamine receptor D1 in renal proximal tubular cells. We investigated the role of G-protein receptor kinase 4 polymorphism in the response to hypertensive therapy in patients with essential hypertension.
  
  
  METHODS
  In a prospective study, we assessed the G-protein receptor kinase 4 polymorphisms R65L, A142V, and A486V in 100 hypertensive patients. We analyzed the association of the 3 gene variants on blood pressure control and response to antihypertensive therapy with single-locus analysis, haplotype analysis, and regression analysis.
  
  
  RESULTS
  Hypertensive individuals with a homozygous double variant of 65 L and 142 V needed significantly more antihypertensive treatment (number of antihypertensives 2.59 vs 1.95, P = 0.043) and especially diuretic therapy (0.82 vs 0.49, P = 0.029) to reach the same mean arterial blood pressure than did homozygous carriers of only 1 variant or heterozygous/wild-type carriers of R65L, A142V, and A486V alleles.
  
  
  CONCLUSIONS
  G-protein receptor kinase 4 polymorphism is associated with antihypertensive treatment response in patients with essential hypertension. Determination of G-protein receptor kinase 4 polymorphism may improve individual antihypertensive blood pressure control in patients with essential hypertension.
authors.affiliation: Division of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland;
authors.forename: Anne M
authors.initials: AM
authors.lastname: Muskalla
authors.affiliation: Division of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland;
authors.forename: Paolo M
authors.initials: PM
authors.lastname: Suter
authors.affiliation: Division of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland; current affiliation: Rheumatology and pain center, Frauenfeld, Switzerland;
authors.forename: Matthias
authors.initials: M
authors.lastname: Saur
authors.affiliation: Division of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland;
authors.forename: Albina
authors.initials: A
authors.lastname: Nowak
authors.affiliation: Division of Clinical Chemistry, University Hospital of Zurich, Zurich, Switzerland; current affiliation: Institute of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland;
authors.forename: Martin
authors.initials: M
authors.lastname: Hersberger
authors.affiliation: Division of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland; current affiliation: Division of Internal Medicine, Spital Linth, Uznach, Switzerland. pierre-alexandre.krayenbuehl@spital-linth.ch.
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Krayenbuehl
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D054771:G-Protein-Coupled Receptor Kinase 4 / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies
chemical_list: D000959:Antihypertensive Agents; D054771:G-Protein-Coupled Receptor Kinase 4; C517855:GRK4 protein, human