Association of genetic variation in the natriuretic peptide system with cardiovascular outcomes

Ellis, Katrina L.; Newton‐Cheh, Christopher; Wang, Thomas J.; Frampton, Chris; Doughty, Rob; Whalley, Gillian A.; Ellis, Chris; Skelton, Lorraine; Davis, N S; Yandle, Tim G.; Troughton, Richard W.; Richards, A. Mark; Cameron, Vicky A.

doi:10.1016/j.yjmcc.2011.01.010

Cited by 52 publications

(51 citation statements)

References 41 publications

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“…Levels of BNP and NT-proBNP vary in relation to heart failure severity but may also be influenced by several other factors. Age, 35 sex, 36 body mass index, 37 and genetic factors [38][39][40] are important confounders, as are concomitant conditions such as atrial fibrillation, pulmonary hypertension, myocardial ischemia, pulmonary embolism, and chronic kidney disease. 41 Patients with heart failure and preserved EF tend to have lower NP levels than those with heart failure and reduced EF, even when the severity of heart failure is similar.…”

Section: Can We Define An Optimal Np Target?mentioning

confidence: 99%

Are Serial BNP Measurements Useful in Heart Failure Management?

Desai

2013

Circulation

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Section: Can We Define An Optimal Np Target?mentioning

confidence: 99%

Are Serial BNP Measurements Useful in Heart Failure Management?

Desai

2013

Circulation

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“…From candidate genetic studies, common variants in the Natriuretic Peptide Precursor Gene B (NPPB) have been reported to be associated, not only with plasma BNP concentrations, but also with BP and hypertension 5 , 6 type 2 diabetes 7, 8 , echocardiographic indices and diastolic dysfunction and congestive heart failure. 9 Thus, in elucidating the genetic architecture of BNP concentration, we are likely to understand the biological basis of these associations.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Analysis of Plasma B–Type Natriuretic Peptide in Blacks

Musani¹,

Fox²,

Kraja³

et al. 2015

Circ Cardiovasc Genet

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Background Numerous experimental studies suggest that B-type natriuretic peptide (BNP) is cardioprotective, yet in clinical studies, higher plasma BNP concentrations have been associated with incident cardiovascular disease and higher left ventricular mass (LVM). Genetic association studies may allow us to determine the true causal directions without confounding by compensatory mechanisms. Methods and Results We performed meta-analysis of two genome-wide association (GWA) results from a total of 2,790 African Americans. We assumed an additive genetic model in association analysis of imputed 2.5 million SNP dosages with residuals generated from multivariable-adjusted logarithmically-transformed BNP controlling for relevant covariates and population stratification. Two loci were genome-wide significant, a candidate gene locus NPPB (rs198389, p-value=1.18×10−09) and novel missense variant in the KLKB1 locus (rs3733402, p-value=1.75×10−11) that explained 0.4% and 1.9% of variation in log BNP concentration, respectively. The observed increase in BNP concentration was proportional to the number of effect allele copies, an average of 8.1 pg/dl increase associated with two allele copies. SNPs in this loci were subsequently cross-checked with GWA results for the aldosterone-to-renin ratio in individuals of European ancestry, and only rs3733402 was genome-wide significant (p<5.0×10−8), suggesting possible shared genetic architecture for these two pathways. Other statistically significant relations for these SNPs included: rs198389 with systolic blood pressure in blacks (COGENT consortium) rs198389 and rs3733402 with LVM in whites (EchoGEN consortium). Conclusions These findings improve our knowledge of the genetic basis of BNP variation in African Americans, demonstrate possible shared allelic architecture for BNP with ARR and motivate further studies of underlying mechanisms.

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“…In a US study of 1,810 coronary disease patients, Ellis et al reported that the minor rs5065 allele was associated with lesser history of hypertension (HT) and a reduced rate of cardiovascular readmission. 19 In a European study, Barbato et al showed that in 1,004 patients with the rs5065 gene undergoing coronary angiography, the minor allele was an independent predictor of acute coronary syndrome and a higher incidence of major adverse cardiac events in patients with stable angina compared with controls. 20 Finally, in 1,623 general population patients in Olmsted County, Minnesota, the minor allele was associated with an increased risk of stroke and a higher prevalence of myocardial infarction (MI).…”

Section: Rs5065 (Tc2238) and Rs5063 (V32m)mentioning

confidence: 99%

Atrial Natriuretic Peptide　― Old But New Therapeutic in Cardiovascular Diseases ―

Ichiki¹,

Burnett²

2017

Circ J

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With the discovery of atrial natriuretic peptide (ANP), the heart as an endocrine organ was established. Basic science revealed that ANP, through the particulate guanylyl cyclase A receptor and cGMP, plays a fundamental role in cardiorenal biology. This work has led to the development of ANP as a therapeutic, especially in heart failure (HF). Human genomics has strengthened our understanding of ANP, revealing specific ANP gene variants that may be associated with biological dysfunction, but also may mediate protective properties, including in metabolic syndrome. Advances in understanding the processing and degradation of ANP molecular forms have resulted in therapeutic breakthroughs, especially inhibition of ANP degradation by neprilysin inhibitors. Although ANP is administered intravenously for acute HF, a novel therapeutic strategy is its chronic delivery by subcutaneous injection. An innovative therapeutic development is engineering to develop ANP-based peptides for chronic use. These interconnected topics of ANP biology and therapeutics will be reviewed in detail.

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Association of genetic variation in the natriuretic peptide system with cardiovascular outcomes

Cited by 52 publications

References 41 publications

Are Serial BNP Measurements Useful in Heart Failure Management?

Are Serial BNP Measurements Useful in Heart Failure Management?

Genome-Wide Association Analysis of Plasma B–Type Natriuretic Peptide in Blacks

Atrial Natriuretic Peptide　― Old But New Therapeutic in Cardiovascular Diseases ―

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Association of genetic variation in the natriuretic peptide system with cardiovascular outcomes

Cited by 52 publications

References 41 publications

Are Serial BNP Measurements Useful in Heart Failure Management?

Are Serial BNP Measurements Useful in Heart Failure Management?

Genome-Wide Association Analysis of Plasma B–Type Natriuretic Peptide in Blacks

Atrial Natriuretic Peptide ― Old But New Therapeutic in Cardiovascular Diseases ―

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Product

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Atrial Natriuretic Peptide　― Old But New Therapeutic in Cardiovascular Diseases ―