Pharmacogenomics of blood pressure response to antihypertensive treatment

PURPOSE IDENTIFICATION: Inter-individual variability in blood pressure response to treatment is well documented, but a clinically useful means to distinguish responders from non-responders has been elusive. With the advent of new technologies and genomic knowledge, more investigators are seeking to identify genetic determinants of blood pressure response to therapy.

We identified studies of candidate polymorphisms from an initial PubMed search using the MESH terms 'Hypertension: Drug Therapy' and 'Genetics' or 'Pharmacogenetics', limiting results to English-language publications on studies in human adults. We further identified specific polymorphisms of interest noted in earlier reviews and performed additional PubMed searches based on these candidate genes. Pertinent studies were further extracted from the references of studies already identified. We focused on clinical trials that measured blood pressure response to a medication or class of medications over a minimum of 4 weeks.

We evaluated studies looking at blood pressure response to commonly used classes of antihypertensive medications by major genetic variants. RESULTS OF ANALYSIS: Although many studies show that blood pressure response to a given class of antihypertensive medications varies by genotype for different polymorphisms, none of the genotypes identified consistently predicted blood pressure response.

Common variants may influence response to diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, but studies of polymorphisms have generally yielded conflicting results. The inclusion of pharmacogenomic studies in large clinical trials and other more innovative investigative methods may provide greater clarity of the potential role for genotyping in the treatment of patients with hypertension.