title: beta1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension.
abstract: OBJECTIVE
  The human beta(1)-adrenergic receptor, an important therapeutic target in cardiovascular diseases, has 2 common functional polymorphisms (Ser49Gly and Gly389Arg). Our study aimed to confirm that beta(1)-adrenergic receptor polymorphisms affect the blood pressure response to metoprolol monotherapy in the Chinese population with hypertension.
  
  
  METHODS
  beta(1)-Adrenergic receptor genotype was determined by polymerase chain reaction-restriction fragment length polymorphism assay for 223 patients with essential hypertension. Sixty-one patients with certain beta(1)-adrenergic receptor diplotypes, 18 for 49Ser389Arg/49Ser389Arg, 15 for 49Ser389Arg/49Gly389Arg, 19 for 49Ser389Gly/49Gly389Arg, and 9 for 49Ser389Gly/49Ser389Gly, were selected from those 61 for measurement of the antihypertensive effect of metoprolol. Patients were given 25 mg metoprolol every 12 hours for 4 weeks. Heart rate and blood pressure were measured weekly for the duration of metoprolol therapy.
  
  
  RESULTS
  The descent of systolic blood pressure after metoprolol administration was significantly different among genotype groups (10.4% +/- 4.0%, 2.8% +/- 4.7%, and 1.1% +/- 1.5% for Arg389Arg, Gly389Arg, and Gly389Gly patients, respectively; P < .001). We also found a similar difference in changes of diastolic blood pressure (6.1% +/- 4.3%, 2.2% +/- 4.2%, and 0.9% +/- 4.0%, respectively; P < .001) and mean arterial pressure (8.1% +/- 3.5%, 2.5% +/- 3.0%, and 1.0% +/- 2.5%, respectively; P > .001) for Arg389Arg, Gly389Arg, and Gly389Gly patients. Ser49Gly variance exhibited a smaller contribution to the antihypertensive effect of metoprolol. Systolic blood pressure decreased significantly in Ser49 homozygous patients compared with Ser49Gly patients (8.4% +/- 3.2% versus 5.3% +/- 5.2%, P = .047). There was a highly significant relationship between diplotype and blood pressure during treatment. Systolic blood pressure significantly decreased in 49Ser389Arg/49Ser389Arg (12.0% +/- 3.8%, P < .001) and 49Ser389Arg/49Gly389Arg (8.4% +/- 5.5%, P < .001) patients, with the decrease in the former being more pronounced (P = .023). We also found a significant decrease in diastolic blood pressure (6.5% +/- 4.7% versus 5.7% +/- 3.2%, respectively; both P < .001) and mean arterial pressure (8.8% +/- 3.2% versus 6.9% +/- 3.7%, respectively; both P < .001) in 49Ser389Arg/49Ser389Arg and 49Ser389Arg/49Gly389Arg patients. However, blood pressure did not change significantly in 49Ser389Gly/49Gly389Arg and 49Ser389Gly/49Ser389Gly patients (all P > .05).
  
  
  CONCLUSIONS
  beta(1)-Adrenergic receptor polymorphism was associated with different blood pressure responses to metoprolol therapy in patients with essential hypertension. 49Ser389Arg/49Ser389Arg and 49Ser389Arg/49Gly389Arg patients were good responders to metoprolol therapy; 49Ser389Arg/49Ser389Arg patients had a larger systolic blood pressure reduction than 49Ser389Arg/49Gly389Arg patients did. 49Ser389Gly/49Gly389Arg and 49Ser389Gly/49Ser389Gly patients were nonresponders to metoprolol antihypertensive therapy.
authors.affiliation: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
authors.forename: Bang-Ning
authors.initials: BN
authors.lastname: Yu
authors.forename: Fang-Hua
authors.initials: FH
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Mo
authors.forename: Gan
authors.initials: G
authors.lastname: Zhou
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002681:China; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011943:Receptors, Adrenergic, beta / Q000235:genetics*
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D008790:Metoprolol