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Journal of Cardiovascular Translational Research

Published in:

01-12-2015

Genetic Factors Influencing B-type Natriuretic Peptide-Mediated Production of Cyclic Guanosine Monophosphate and Blood Pressure Effects in Heart Failure Patients

Authors: David E. Lanfear, Jia Li, Raza Abbas, Ricoung She, Badri Padhukasahasram, Ramesh C. Gupta, David Langholz, W. H. Wilson Tang, L. Keoki Williams, Hani N. Sabbah, Sheryl L. Chow

Published in: Journal of Cardiovascular Translational Research | Issue 9/2015

Abstract

Natriuretic peptides (NPs) represent a critical pathway in heart failure (HF). We explored genetic determinants of pharmacodynamic effects of B-type NP (BNP) and changes in plasma cyclic guanosine monophosphate (cGMP) and blood pressure (BP). HF patients (n = 135) received recombinant human BNP (nesiritide) at standard doses, and plasma cGMP levels were measured at baseline and during infusion. We tested the association of 119 single nucleotide polymorphisms (SNPs) in 4 candidate genes (NPR1, NPR2, NPR3, and membrane metallo-endopeptidase (MME)) with the change in cGMP and BP. Gene-based testing for association of genetic variation with endpoints was significant only for MME. Upon individual SNP testing, two loci in MME were associated with ΔcGMP; another (rs16824656) showed association with BP change. In summary, the pharmacodynamic effects of BNP vary substantially in HF patients and are associated with genetic variation in MME. MME genetic variation may be an important determinant of NP-mediated effects in humans.

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Title: Genetic Factors Influencing B-type Natriuretic Peptide-Mediated Production of Cyclic Guanosine Monophosphate and Blood Pressure Effects in Heart Failure Patients
Authors: David E. Lanfear
Jia Li
Raza Abbas
Ricoung She
Badri Padhukasahasram
Ramesh C. Gupta
David Langholz
W. H. Wilson Tang
L. Keoki Williams
Hani N. Sabbah
Sheryl L. Chow
Publication date: 01-12-2015
Publisher: Springer US
Published in: Journal of Cardiovascular Translational Research / Issue 9/2015
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-015-9660-2

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