Polymorphisms ofEDNRB,ATG, andACEgenes in salt-sensitive hypertensionThis article is one of a selection of papers published in the special issue (part 2 of 2) on Forefronts in Endothelin.

Caprioli, Jessica; Mele, Caterina; Mossali, Chiara; Gallizioli, Laura GallizioliL.; Giacchetti, Gilberta; Noris, Marina; Remuzzi, Giuseppe; Benigni, Ariela

doi:10.1139/y08-045

Cited by 35 publications

(5 citation statements)

References 26 publications

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“…We previously demonstrated that SNPs in GRK4 are highly associated with salt-sensitive hypertension in Japanese 28 and Italians 29 which was recapitulated in transgenic mice expressing the human GRK4 variants 2 . Additional polymorphisms in α-adducin (ADD1), angiotensin converting enzyme (ACE), angiotensinogen (AGT), cytochrome P450/11B polypeptide 2 (CYP11B2), G-protein β3 subunit (GNβ3), and neural precursor cell expressed developmentally down-regulated 4-like protein (NEDD4L) have been linked to salt-sensitive hypertension 2 , 30 . Since it is of interest to determine if candidate genes are associated with salt-sensitivity, independently of hypertension, we examined polymorphisms in a Caucasian cohort, containing subjects who were both NT and HT that had been phenotyped for salt-sensitivity using controlled diets.…”

Section: Discussionmentioning

confidence: 99%

“…Building on this evidence, SLC4A5 was identified as a candidate hypertension susceptibility gene using several combined positional candidate gene methods 34 . Selected single nucleotide polymorphisms at positions SLC4A5 (rs6731545), SLC4A5 A/C (rs1017783) and SLC4A5 A/G (rs7571842) were associated with elevated heart rate and BP in both Caucasians and African-Americans 15,16,30 . Our results are consistent in that the allele associated with increased BP in Hunt et al 15 was also our risk allele (A) for salt sensitivity of BP.…”

Section: Discussionmentioning

confidence: 99%

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Salt Sensitivity of Blood Pressure Is Associated With Polymorphisms in the Sodium-Bicarbonate Cotransporter

et al. 2012

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Past studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt-sensitivity of blood pressure (BP) in 185 Caucasians consuming an isocaloric constant diet with a randomized order of 7 days low Na+ (10 mmol/d) and 7 days high Na+ (300 mmol/d) intake. Salt-sensitivity was defined as a ≥7mm Hg increase in mean arterial pressure (MAP) during a randomized transition between high and low Na+ diet. A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt-sensitivity revealed three variants that associated with salt-sensitivity, two in SLC4A5 (P <0.001), and one in GRK4 (P = 0.020). Of these, two SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These two SNPs had P values of 1.0×10−4 and 3.1×10−4 with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for BMI and age, (P = 8.9×10−5 and 2.6×10−4 and odds ratios 0.210 and 0.286, respectively). Further, the association of these SNPS with salt-sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt-sensitivity [rs7571842 (P=1.2×10−5); rs1017783 (P=1.1×10−4)]. In conclusion, SLC4A5 variants are strongly associated with salt-sensitivity of BP in two separate Caucasian populations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Salt Sensitivity of Blood Pressure Is Associated With Polymorphisms in the Sodium-Bicarbonate Cotransporter

et al. 2012

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“…In this study, in regard to the nutritional status, serum albumin and normal protein catabolism rate (nPCR) did not significantly differ among the three subgroups. Several studies have reported a relationship between ACE I/D polymorphism and salt sensitivity [ 29 ]. Salt sensitivity is a measure of how blood pressure responds to salt intake.…”

Section: Discussionmentioning

confidence: 99%

Influence of ACE I/D Polymorphism on Circulating Levels of Plasminogen Activator Inhibitor 1, D-Dimer, Ultrasensitive C-Reactive Protein and Transforming Growth Factor β1 in Patients Undergoing Hemodialysis

et al. 2016

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BackgroundThere is substantial evidence that chronic renal and cardiovascular diseases are associated with coagulation disorders, endothelial dysfunction, inflammation and fibrosis. Angiotensin-Converting Enzyme Insertion/Deletion polymorphism (ACE I/D polymorphism) has also be linked to cardiovascular diseases. Therefore, this study aimed to compare plasma levels of ultrassensible C-reactive protein (usCRP), PAI-1, D-dimer and TGF-β1 in patients undergoing HD with different ACE I/D polymorphisms.MethodsThe study was performed in 138 patients at ESRD under hemodialysis therapy for more than six months. The patients were divided into three groups according to the genotype. Genomic DNA was extracted from blood cells (leukocytes). ACE I/D polymorphism was investigated by single polymerase chain reaction (PCR). Plasma levels of D-dimer, PAI-1 and TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA), and the determination of plasma levels of usCRP was performed by immunonephelometry. Data were analyzed by the software SigmaStat 2.03.ResultsClinical characteristics were similar in patients with these three ACE I/D polymorphisms, except for interdialytic weight gain. I allele could be associated with higher interdialytic weight gain (P = 0.017). Patients genotyped as DD and as ID had significantly higher levels of PAI-1 than those with II genotype. Other laboratory parameters did not significantly differ among the three subgroups (P = 0.033). Despite not reaching statistical significance, plasma levels of usCRP were higher in patients carrying the D allele.ConclusionACE I/D polymorphisms could be associated with changes in the regulation of sodium, fibrinolytic system, and possibly, inflammation. Our data showed that high levels of PAI-1 are detected when D allele is present, whereas greater interdialytic gain is associated with the presence of I allele. However, further studies with different experimental designs are necessary to elucidate the mechanisms involved in these associations.

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“…While the relationship between genetic contributors to hypertension in the SHR and hypertension susceptibility genes in humans remains incompletely understood, six of the seven genes we identified as candidates in the SHR have been reported to contain polymorphisms that associate with hypertension in humans [Chga (25), Comt (50–52), Dbh (37,38), Ednrb (53), Npy (54) and Pnmt (40,41); none has been reported in Etfdh]. Study of these genes in the SHR might provide insight into the genetic and molecular basis of human hypertension.…”

Section: Discussionmentioning

confidence: 99%

Systematic polymorphism discovery after genome-wide identification of potential susceptibility loci in a hereditary rodent model of human hypertension

2011

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Genetic strategies such as linkage analysis and quantitative trait locus (QTL) mapping have identified a multitude of loci implicated in the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR). While several candidate genetic regions have been identified in the SHR and its control, the Wistar–Kyoto rat (WKY), systematic follow-up of candidate identification with polymorphism discovery has not been widespread. In the current report, we develop a data-mining strategy to identify candidate genes for hypertension in the SHR, and then sequence each gene in the SHR and WKY strains. We integrate blood pressure QTL data, microarray data and data-mining methods. First, we determined the set of genes differentially expressed in SHR and WKY adrenal glands. Next, the chromosomal position of all differentially expressed genes was compared with peak marker position of all reported SHR blood pressure QTLs. We also identified the set of differentially expressed genes with the most extreme fold-change. Finally, the QTL positional candidates and the genes with extreme differential expression were proposed as candidate genes if they had biologically plausible roles in hypertensive pathology. We identified seven candidate genes that merit resequencing (catechol-O-methyltransferase [Comt], chromogranin A [Chga], dopamine beta-hydroxylase [Dbh], electron transferring flavoprotein dehydrogenase [Etfdh], endothelin receptor type B [Ednrb], neuropeptide Y [Npy] and phenylethanolamine-N-methyltransferase [Pnmt]), and then discovered polymorphism in four of these seven candidate genes. Chga is proposed as the strongest candidate for additional functional investigation. Our method for candidate gene identification is portable and can be applied to microarray data from any tissue, in any disease model with a QTL database.

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Polymorphisms ofEDNRB,ATG, andACEgenes in salt-sensitive hypertensionThis article is one of a selection of papers published in the special issue (part 2 of 2) on Forefronts in Endothelin.

Cited by 35 publications

References 26 publications

Salt Sensitivity of Blood Pressure Is Associated With Polymorphisms in the Sodium-Bicarbonate Cotransporter

Salt Sensitivity of Blood Pressure Is Associated With Polymorphisms in the Sodium-Bicarbonate Cotransporter

Influence of ACE I/D Polymorphism on Circulating Levels of Plasminogen Activator Inhibitor 1, D-Dimer, Ultrasensitive C-Reactive Protein and Transforming Growth Factor β1 in Patients Undergoing Hemodialysis

Systematic polymorphism discovery after genome-wide identification of potential susceptibility loci in a hereditary rodent model of human hypertension

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