title: Association of common polymorphisms in β1-adrenergic receptor with antihypertensive response to carvedilol.
abstract: OBJECTIVE
  Marked interpatient variability exists in the blood pressure response to carvedilol, a nonselective β-blocker. Here we evaluated the influence of 4 common polymorphisms in genes of the β-adrenergic receptor on the antihypertensive efficacy of carvedilol in patients in a double-blinded monotherapy study.
  
  
  METHODS
  Eighty-seven subjects with uncomplicated essential hypertensive (49% men; age = 52.2 ± 11.1 years) from Jilin province of China were enrolled in the study, and 5 of them discontinued the treatment due to adverse effects. Both systolic and diastolic blood pressures (DBPs) were measured before and after 7 days of treatment with carvedilol (10 mg/d). Genotypes of the β1-adrenergic receptor (ADRB1 Ser49Gly and Arg389Gly) and β2-adrenergic receptor (ADRB2 Gly16Arg and Glu27Gln) were determined by polymerase chain reaction with restriction fragment length polymorphism.
  
  
  RESULTS
  Patients homozygous for ADRB1 Arg389 had an approximately 4-fold greater reduction in DBPs than those homozygous for ADRB1 Gly389 (10.61 vs. 2.62 mm Hg, P = 0.013). The ADRB1 haplotype was also a significant predictor of response, as patients with the Gly49Arg389/Ser49Arg389 haplotype pair had a 5.7-fold greater reduction in DBPs than those homozygous for the Ser49Gly389 haplotype (16.11 vs. 2.83 mm Hg, P = 0.0055). An association was not found between ADRB2 polymorphism and carvedilol responsiveness in antihypertensive therapy.
  
  
  CONCLUSIONS
  This study provides the first evidence to support that ADRB1 polymorphisms play an important role in the DBPs response to carvedilol treatment in patients with essential hypertension.
authors.affiliation: *School of Life Science, Jilin University, Changchun, China; †Key-Lab for Evolution of Past Life and Environment in Northeast Asia, Ministry of Education, Jilin University, Changchun, China; ‡Division of Nephrology, The First Hospital of Jilin University, Changchun, China; and §Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Si
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Xiaoshuai
authors.initials: X
authors.lastname: Chen
authors.forename: Mingqiu
authors.initials: M
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D002681:China; D000075222:Essential Hypertension; D005260:Female; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011412:Propanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*
chemical_list: C547787:ADRB1 protein, human; D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D000077261:Carvedilol