Dataset Information

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

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 (p?=?0.007) 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, p?=?0.03). 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.

SUBMITTER: Pereira NL

PROVIDER: S-EPMC3899045 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

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

Pereira Naveen L NL Redfield Margaret M MM Scott Christopher C Tosakulwong Nirubol N Olson Timothy M TM Bailey Kent R KR Rodeheffer Richard J RJ Burnett John C JC

PloS one 20140122 1

<h4>Objectives</h4>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.<h4>Background</h4>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 i ...[more]

PMID: 24465655

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Project description:IntroductionChagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the role of diastolic dysfunction, abnormal myocardial strain and elevated brain natriuretic peptide (BNP) in the early identification of cardiac involvement in Chagas disease.Methodology/principal findingsFifty-four patients divided into 3 groups--group 1 (undetermined form: positive serology without ECG or 2D-echocardiographic abnormalities; N = 32), group 2 (typical ECG abnormalities of Chagas disease but normal 2D-echocardiography; N = 14), and group 3 (regional wall motion abnormalities, left ventricular [LV] end-diastolic diameter >55 mm or LV ejection fraction <50% on echocardiography; N?=?8)--and 44 control subjects were studied. Patients with significant non-cardiac diseases, other heart diseases and previous treatment with benznidazol were excluded. The median age was 37 (20-58) years; 40% were men. BNP levels, longitudinal and radial myocardial strain and LV diastolic dysfunction increased progressively from group 1 to 3 (p for trend <0.01). Abnormal BNP levels (>37 pg/ml) were noted in 0%, 13%, 29% and 63% in controls and groups 1 to 3, respectively. Half of patients in the undetermined form had impaired relaxation patterns, whereas half of patients with ECG abnormalities suggestive of Chagas cardiomyopathy had normal diastolic function. In group 1, BNP levels were statistically higher in patients with diastolic dysfunction as compared to those with normal diastolic function (27 ± 26 vs. 11 ± 8 pg/ml, p = 0.03).Conclusion/significanceIn conclusion, the combination of diastolic function and BNP measurement adds important information that could help to better stratify patients with Chagas disease.

Dataset Information

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

Objectives

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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