Polymorphisms within the atrial natriuretic peptide gene in essential hypertension

Rutledge, David R.; Sun, Yanmei; Ross, Edward A.

doi:10.1097/00004872-199509000-00003

Cited by 71 publications

(48 citation statements)

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“…An HpaII-polymorphism in intron 2 of the ANP gene is more frequently observed in salt-sensitive hypertensive African Americans (50%) compared with normotensive subjects (3%) or with white patients with EH (15%). 108,109 For GC-A, the association between a functional deletion mutation in the promoter region of the human GC-A gene, decreased receptor expression, and EH as well as ventricular hypertrophy has been shown in the Japanese population 110 but not in European patients with EH. 111 Knowles et al 112 recently identified 10 additional polymorphic sites in the noncoding sequence of GC-A and, by transient expression analysis, demonstrated that they can alter GC-A expression as much as 2-fold.…”

Section: Relevance Of Alterations In the Anp/gc-a System To Cardiovasmentioning

confidence: 99%

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

Kühn

2003

Circulation Research

239

161

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Abstract-Besides soluble guanylyl cyclase (GC), the receptor for NO, there are at least seven plasma membrane enzymes that synthesize the second-messenger cGMP. All membrane GCs (GC-A through GC-G) share a basic topology, which consists of an extracellular ligand binding domain, a short transmembrane region, and an intracellular domain that contains the catalytic (GC) region. Although the presence of the extracellular domain suggests that all these enzymes function as receptors, specific ligands have been identified for only three of them (GC-A through GC-C). GC-A mediates the endocrine effects of atrial and B-type natriuretic peptides regulating arterial blood pressure and volume homeostasis and also local antihypertrophic actions in the heart. GC-B is a specific receptor for C-type natriuretic peptide, having more of a paracrine function in vascular regeneration and endochondral ossification. GC-C mediates the effects of guanylin and uroguanylin on intestinal electrolyte and water transport and on epithelial cell growth and differentiation. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have an important role in phototransduction. Finally, the functions of GC-D (located in the olfactory neuroepithelium) and GC-G (expressed in highest amounts in lung, intestine, and skeletal muscle) are completely unknown. This review discusses the structure and functions of membrane GCs, with special emphasis on the physiological endocrine and cardiac functions of GC-A, the regulation of hormone-dependent GC-A activity, and the relevance of alterations of the atrial natriuretic peptide/GC-A system to cardiovascular diseases. (Circ Res. 2003;93:700-709.)

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Section: Relevance Of Alterations In the Anp/gc-a System To Cardiovasmentioning

confidence: 99%

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

Kühn

2003

Circulation Research

239

161

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“…On the other hand, disruption of the guanylate cyclase-A gene results in salt-resistant hypertension in mice (65). In humanhypertension, mutations in the ANP gene are observed more prominently among African hypertensive individuals (66).…”

Section: Atrial Natriuretic Factor or Peptidementioning

confidence: 99%

Recent Aspects in the Genetic Renal Mechanisms Involved in Hypertension.

1999

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The kidney plays an important role in the blood pressure regulation primarily by modulating tubular sodium reabsorption. Various hormones, vasoactive peptides, autacoids and transporters or channels in renal tubules are involved in this process. Genes associated with renal tubular sodium handling are possibly related to the development of hypertension. Genes of the renin-angiotensin-aldosterone system are thought to be especially important as causal genes of hypertension. Na-K-ATPase, biochemically equal to Na pump, exists on the basolateral membrane of renal epithelial cells. It plays a central role in Na reabsorption and creates a driving force for transepithelial transport. Na-K-ATPaseactivity is regulated by adducin, a membrane-bound skeletal protein, as well as by several hormones such as dopamine, endogenous ouabain-like factor or cytochrome P450 metabolites. Genes of these factors involved in Na-K-ATPaseregulation should be related to the development of hypertension. The endothelin system, atrial natriuretic peptide and nitric oxide regulate the tonus of blood vessels as well as renal sodiumexcretion. Several reports have indicated that genes of these substances are crucial in the pathogenesis of hype rtension. (Internal Medicine 38: 919-926, 1999)

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“…6 In humans, few studies revealing controversial findings are available on the association between hypertension and polymorphisms within the NPPA gene. [7][8][9][10] The large sample size and long follow-up of the Women's Health Study provide a unique opportunity to prospectively analyze genetic influences on multifactorial disorders. We, therefore, tested the hypothesis that NPPA gene polymorphisms are significantly associated with blood pressure progression and incident hypertension in initially healthy, middle-aged women.…”

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confidence: 99%

Natriuretic Peptide Precursor A Gene Polymorphisms and Risk of Blood Pressure Progression and Incident Hypertension

et al. 2007

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Abstract-We tested the hypothesis that natriuretic peptide precursor A gene polymorphisms are significantly associated with blood pressure progression and incident hypertension among healthy, middle-aged women. We performed a prospective cohort study among 18 437 white women participating in the Women's Health Study who were free of hypertension at baseline. Two previously characterized single nucleotide polymorphisms within the natriuretic peptide precursor A gene (rs5063 GϾA and rs5065 TϾC) were genotyped. Blood pressure progression at 48 months and incident hypertension during the entire follow-up according to the different genotypes and inferred haplotypes were assessed by logistic regression and Cox proportional hazards models, respectively. n a Western population, the cumulative lifetime risk of developing hypertension approaches 90%. 1 Although obesity and other environmental factors 2 substantially contribute to the high incidence of hypertension, twin studies suggest that, in human beings, up to one third of the interindividual variability of blood pressure is heritable. 3 Thus, it is important to understand genetic influences on blood pressure and hypertension. However, genetic studies of multifactorial disorders such as hypertension have proven difficult because of the multiplicity of genes underlying complex phenotypes and the modest effect of an individual polymorphism or gene.Atrial natriuretic peptide plays a significant role in the regulation of vascular tone and sodium homeostasis. 4 Experimental studies showed that underexpression of the natriuretic peptide precursor A gene (NPPA; gene ID 4878, chromosome location 1p36.21) is associated with elevated blood pressure in transgenic mice, 5 whereas overexpression of NPPA leads to decreased blood pressure levels. 6 In humans, few studies revealing controversial findings are available on the association between hypertension and polymorphisms within the NPPA gene. [7][8][9][10] The large sample size and long follow-up of the Women's Health Study provide a unique opportunity to prospectively analyze genetic influences on multifactorial disorders. We, therefore, tested the hypothesis that NPPA gene polymorphisms are significantly associated with blood pressure progression and incident hypertension in initially healthy, middle-aged women. Methods ParticipantsAll of the study subjects were participants of the Women's Health Study, a completed randomized trial evaluating the risks and benefits of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer among female health professionals. Details of the study design have been described previously. [11][12][13] Briefly, information on baseline variables was collected using mailed questionnaires. Follow-up questionnaires asking participants about study outcomes and other information were sent every 6

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Polymorphisms within the atrial natriuretic peptide gene in essential hypertension

Cited by 71 publications

References 0 publications

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

Recent Aspects in the Genetic Renal Mechanisms Involved in Hypertension.

Natriuretic Peptide Precursor A Gene Polymorphisms and Risk of Blood Pressure Progression and Incident Hypertension

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