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

OBJECTIVES: 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) 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 .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.