Pharmacogenomics of the Natriuretic Peptide System in Heart Failure

Heart failure (HF) continues to be a public health burden despite advances in therapy, and the natriuretic peptide (NP) system is clearly of critical importance in this setting, spawning valuable diagnostic and prognostic testing, such as B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), as well as current and future therapeutics, including recombinant natriuretic peptides (e.g., carperitide, nesiritide) and recently sacubitril, which inhibits the key clearance mechanism for NPs. This article intends to summarize the existing evidence for the role of NP system genetic variation on cardiovascular phenotypes relevant to HF with particular focus on the potential impact on pharmacologic therapies.

Several genes in NP system have been interrogated, in many cases genetic variation impacting protein quantity and function or related disease states. Recent data supports genetic variants potentially impacting pharmacokinetics or dynamics of medications targeting the pathway. Growing evidence indicates the importance of genetic variation to the functioning of the NP system and its pharmacologic manipulation.