• polymorphisms
• pharmacogenetics
• hypertension
• beta-blocker

Genetic polymorphisms in adrenergic receptors (AR) may contribute to interindividual differences in antihypertensive therapy response. Since carvedilol is a nonselective betablocker, we sought to evaluate whether its blood pressure lowering effect is related to functionally relevant alpha- and beta-AR polymorphisms in the genes coding for these receptors.
82 newly recognised, never treated hypertensive patients (47±11 years, 62 men) underwent baseline examinations including local measurement of systolic and diastolic arterial pressure (SAP and DAP) and 24hour ambulatory blood pressure monitoring (ABPM). After 4-week treatment period with carvedilol (12,5 mg every 12 hours, “case group”) or amlodipine (5 mg in the morning, “control group”), BP evaluations were repeated. Patients were genotyped for the following polymorphisms: Ser49Gly and Arg389Gly of the beta1-AR; Arg19Cys in the promoter region, Arg16Gly and Gln27Glu in the coding region of the beta2-AR; Arg492Cys of the alpha1A-AR.
At baseline, patients carrying homozygosity for Arg389 variant of the beta1-AR showed clinical SAP and DAP, 24hours and day-time SAP and DAP values significantly higher than 389Gly carriers. After carvedilol administration, Arg389Arg patients had a significantly greater reduction in blood pressure values, also at multivariate analysis. On the other hand, patients treated with amlodipine did not show significant differences in BP reduction stratified according to beta1-AR Arg389Gly genotypes. We did not find any difference as far as the other polymorphisms are concerned.
In conclusion, beta1-AR Arg389Gly polymorphism is both a modulating factor of baseline blood pressure and a relevant determinat of carvedilol antihypertensive effect in patients with essential hypertension.