Prediction of patient responses to antihypertensive drugs using genetic polymorphisms: investigation of renin-angiotensin system genes

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Abstract

Objective To investigate whether the M235T polymorphism of the angiotensinogen (AGT) gene and the insertion/deletion (I/D) polymorphism of the angiotensin-1 converting enzyme (ACE) gene predict blood pressure response to different antihypertensive agents.

Design Sixty-three patients with untreated essential hypertension were randomly assigned in a placebocontrolled crossover comparison to atenolol 50 mg once daily, lisinopril 10mg once daily and nifedipine SR 20mg twice daily, and the effect on blood pressure was assessed by ambulatory blood pressure monitoring (ABPM), In a further 44 patients, placebo-controlled ABPM data were available after treatment with a single agent (atenolol 50 mg once daily in 16 cases and lisinopril 10mg once daily in 28 cases). The change in systolic and diastolic blood pressure achieved by each agent was analysed for association with genotypes at the AGT and ACE gene loci.

Methods Polymerase chain reaction (PCR) amplification of genomic DNA from each individual was used to identify the I/D polymorphism of the ACE gene. The M235T polymorphism of the AGT gene was detected by Tf/)111I digestion of PCR product.

Results There was no significant association 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 attributed to the polymorphisms analysed at the ACE and AGT loci.

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