PREDICTION OF PATIENT RESPONSES TO ANTIHYPERTENSIVE DRUGS USING GENETIC POLYMORPHISMS - INVESTIGATION OF RENIN-ANGIOTENSIN SYSTEM GENES

Objective To investigate whether the M235T polymorphism of the angiote nsinogen (AGT) gene and the insertion/deletion (I/D) polymorphism of t he angiotensin-l converting enzyme (ACE) gene predict blood pressure r esponse to different antihypertensive agents. Design Sixty-three patie nts with untreated essential hypertension were randomly assigned in a placebo-controlled crossover comparison to atenolol 50mg once daily, l isinopril 10mg once daily and nifedipine SR 20mg twice daily, and the effect on blood pressure was assessed by ambulatory blood pressure mon itoring (ABPM). In a further 44 patients, placebo-controlled ABPM data were available after treatment with a single agent (atenolol 50mg onc e daily in 16 cases and lisinopril 10mg once daily in 28 cases). The c hange in systolic and diastolic blood pressure achieved by each agent was analysed for association with genotypes at the AGT and ACE gene lo ci. Methods Polymerase chain reaction (PCR) amplification of genomic D NA from each individual was used to identify the I/D polymorphism of t he ACE gene, The M235T polymorphism of the AGT gene was detected by Tt hlllI digestion of PCR product, Results There was no significant assoc iation between response to any drug and either the AGT M235T or ACE I/ D polymorphisms, Conclusions The large variability between individuals in the observed blood pressure response to these agents cannot be att ributed to the polymorphisms analysed at the ACE and AGT loci.