Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renalase, a novel flavin adenine dinucleotide-dependent amine oxidase, is secreted by the kidney, degrades circulating catecholamines, and modulates cardiac function and systemic blood pressure (BP). Its discovery may provide novel insights into the mechanisms of BP regulation and the pathogenesis of essential hypertension (EH). We designed a two-stage case-control study to investigate whether the renalase gene harbored any genetic variants associated with EH in the northern Han Chinese population. From the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA in China), 1,317 hypertensive cases and 1,269 normotensive controls were recruited. These total 2,586 subjects were taken as the main study population in this study. In stage 1, all the eight selected single nucleotide polymorphisms (SNPs) of the renalase gene were genotyped and tested within a subsample (503 cases and 490 controls) of the main study population. By single locus analyses, three SNPs, rs2576178, rs2296545, and rs2114406, showed significant associations with EH (P < 0.05). In stage 2, these three SNPs were genotyped on the remaining individuals and analyzed using all the individuals. After Bonferroni correction for multiple comparisons, the associations of rs2576178 and rs2296545 with EH were still significant in stage 2. The cases had higher frequencies of rs2576178 G allele and rs2296545 C allele than the controls (0.55 versus 0.49, P < 0.0001; 0.61 versus 0.55, P < 0.0001). Particularly, under the codominant model, the adjusted odds ratios for rs2576178 GG genotype and rs2296545 CC genotype were 1.58 (95% CI, 1.25 to 2.00; P = 0.0002) and 1.61 (95% CI, 1.26 to 2.04; P = 0.0002), respectively. We also found risk-associated haplotypes and diplotypes, which further confirmed the significant association between the renalase gene and EH. These findings may provide novel genetic susceptibility markers for EH and lead to a better understanding of EH pathophysiology. In addition, further replications in other populations and functional studies would be warranted.
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PMID:Renalase gene is a novel susceptibility gene for essential hypertension: a two-stage association study in northern Han Chinese population. 1721 3

The renalase pathway is a previously unrecognized mechanism for regulating cardiac function and blood pressure. In this pathway, renalase, a novel secreted amine oxidase that is inactive at baseline, is rapidly turned on ( ~ 10 fold increase) by either a modest increase in blood pressure or by brief surges in plasma catecholamines. The active enzyme degrades circulating catecholamines, causing a significant fall in blood pressure. Plasma catecholamines not only activate renalase enzymatic activity but also lead to a 3-4 fold stimulation of renalase secretion. The renalase knockout mouse (KO) is hypertensive and exquisitely sensitive to cardiac ischemia. Abnormalities in the renalase pathway are present in animal models of chronic kidney disease (CKD) and hypertension. Two single-nucleotide polymorphisms (SNPs) in the renalase gene were found to be associated with essential hypertension in man. Blood renalase levels are inversely correlated with glomerular filtration rate (GFR) and are markedly reduced in patients with end-stage kidney disease (ESRD). We hypothesize that renalase is secreted into blood by the kidney (although also expressed in heart, skeletal muscle, and small intestine) and plays a key role in regulating blood pressure and cardiovascular function, and that abnormalities in the renalase pathway contribute to the heightened cardiovascular risks observed in patients with CKD.
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PMID:Regulation of blood pressure and cardiovascular function by renalase. 1947 22

Renalase is an amine oxidase expressed in kidney, heart, liver, and brain that metabolizes catecholamines. Tissue and plasma levels are decreased in models of hypertension and chronic kidney disease. Its expression is modulated by salt intake, and urinary renalase may regulate catecholamines levels and effect renal sodium and phosphate transport. The renalase knockout mouse is hypertensive in the absence of significant changes in renal function. Sympathetic tone is increased as evidenced by elevated plasma and urine catecholamines. Studies in humans with resistant hypertension indicate that plasma renalase levels are inversely associated with systolic blood pressure. Additionally, a functional mutation in renalase (Glu37Asp), known to be associated with essential hypertension, also predicts more severe cardiac hypertrophy and dysfunction. Lastly, a single dose of recombinant renalase administered subcutaneously to rats with chronic kidney disease or to Spontaneously Hypertensive Stroke Prone rats significantly decreases blood pressure for more than 24 h. Available data suggest that renalase deficiency is associated with increased sympathetic tone and resistant hypertension, and recombinant renalase is a potent antihypertensive agent that may provide a valuable option for treating hypertension in chronic kidney disease.
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PMID:Novel insights into the physiology of renalase and its role in hypertension and heart disease. 2142 26