Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2014 Jan 22;9(1):e85708. doi: 10.1371/journal.pone.0085708. eCollection 2014.

A functional genetic variant (N521D) in natriuretic peptide receptor 3 is associated with diastolic dysfunction: the prevalence of asymptomatic ventricular dysfunction study.

Author information

1
Division of Cardiovascular Diseases and Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
2
Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America.
3
Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.

Abstract

OBJECTIVES:

To evaluate the impact of a functional genetic variant in the natriuretic peptide clearance receptor, NPR3, on circulating natriuretic peptides (NPs) and myocardial structure and function in the general community.

BACKGROUND:

NPR3 plays an important role in the clearance of NPs and through direct signaling mechanisms modulates smooth muscle cell function and cardiac fibroblast proliferation. A NPR3 nonsynonymous single nucleotide polymorphism (SNP) rs2270915, resulting in a N521D substitution in the intracellular catalytic domain that interacts with Gi could affect receptor function. Whether this SNP is associated with alterations in NPs levels and altered cardiac structure and function is unknown.

METHODS:

DNA samples of 1931 randomly selected residents of Olmsted County, Minnesota were genotyped. Plasma NT-proANP1-98, ANP1-28, proBNP1-108, NT-proBNP1-76, BNP1-32 and BNP3-32 levels were measured. All subjects underwent comprehensive echocardiography.

RESULTS:

Genotype frequencies for rs2270915 were as follows: (A/A 60%, A/G 36%, G/G 4%). All analyses performed were for homozygotes G/G versus wild type A/A plus the heterozygotes A/G. Diastolic dysfunction was significantly more common (pā€Š=ā€Š0.007) in the homozygotes G/G (43%) than the A/A+A/G (28%) group. Multivariate regression adjusted for age, sex, body mass index and hypertension demonstrated rs2270915 to be independently associated with diastolic dysfunction (odds ratio 1.94, pā€Š=ā€Š0.03). There was no significant difference in NPs levels between the 2 groups suggesting that the clearance function of the receptor was not affected.

CONCLUSIONS:

A nonsynonymous NPR3 SNP is independently associated with diastolic dysfunction and this association does not appear to be related to alterations in circulating levels of natriuretic peptides.

PMID:
24465655
PMCID:
PMC3899045
DOI:
10.1371/journal.pone.0085708
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center