There is a growing literature on the potential prospective use of genome information to enhance success in finding new medicines. An example of a prospective efficacy of pharmacogenetic and pharmacogenomics is the detection and impact of
adducin polymorphism on
hypertension.
Adducin is a heterodimeric cytoskeleton
protein, the three subunits of which are encoded by genes (ADD1, ADD2, and ADD3) that map to three different chromosomes. A long series of parallel studies in the Milan hypertensive rat strain model of
hypertension and humans indicated that an altered
adducin function might cause
hypertension through an enhanced constitutive tubular
sodium reabsorption. In particular, six linkage studies, 18 of 20 association studies, and four of five follow-up studies that measured organ damage in hypertensive patients support the clinical impact of adducing polymorphism. As many modulatory genes and environment affect the
adducin activity, the context must be taken into account to measure the clinical effect size of adducins. Pharmacogenomics is giving an important contribution to this end. In particular, the selective advantages of
diuretics in preventing
myocardial infarction and
stroke over other
antihypertensive therapies that produce a similar BP reduction in carriers of the mutated
adducin may support new strategies that aim to optimize the use of
antihypertensive agents for the prevention of
hypertension-associated organ damage.