β1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension*.

Objectives: The human β₁-adrenergic receptor, an important therapeutic target in cardiovascular diseases, has 2 common functional polymorphisms (Ser49Gly and Gly389Arg). Our study aimed to confirm that β₁-adrenergic receptor polymorphisms affect the blood pressure response to metoprolol monotherapy in the Chinese population with hypertension.Methods: β₁-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 β₁-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: β₁-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.Clinical Pharmacology & Therapeutics (2006) 80, 23–32; doi:10.1016/j.clpt.2006.03.004 [ABSTRACT FROM AUTHOR]