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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Essential hypertension is considered to be a typical complex disease with multifactorial etiology, which leads to inconsistent findings in genetic studies. One possibility of failure to replicate some single-locus results is that the underlying genetics of hypertension are not only based on multiple genes with minor effects but also on gene-gene interactions. To test this hypothesis, a case-control study was constructed in Chinese subjects, detecting both single locus and multilocus effects. Eleven candidate genes were selected from biochemical pathways that have been implicated in the development and progression of hypertension, and 33 polymorphisms were evaluated in 503 hypertension patients and 490 age- and gender-matched controls. Single-locus associations, using traditional logistic regression analyses, and multilocus associations, using classification and regression trees and multivariate adaptive regression splines, were both explored in this study. Final models were selected using either Bonferroni correction or cross-validation. Three polymorphisms, TH*rs2070762, ADRB2*Q27E, and GRK4*A486V, were found to be independently associated with essential hypertension in Chinese subjects. In addition to these individual predictors, a potential interaction of CYP11B2-AGTR1 is also involved in the etiology of hypertension. These findings support the multigenic nature of the etiology of essential hypertension and propose a potential gene-gene interactive model for future studies.
Hypertension 2006 Jun
PMID:Association study with 33 single-nucleotide polymorphisms in 11 candidate genes for hypertension in Chinese. 1663 98

The objective of this study was to evaluate the impact of variations of the angiotensinogen (AGT) and angiotensin II type I receptor (AGTR1) genes on progression of blood pressure (BP) and left ventricular mass (LVM) in multiethnic youth. The study was longitudinal involving 581 European American (EA) and African American (AA) youth with 12 assessments over a 15-year period. AGT M235T and three AGTR1 polymorphisms (C-521T, L191L and A1166C) were genotyped and individual growth curve modeling analyses were conducted. Single nucleotide polymorphism (SNP) analyses found a significant 3-way interaction between M235T, ethnicity and gender on BP levels. Systolic BP (SBP) levels were 5.8 mmHg (p = .00003) and diastolic BP (DBP) levels were 2.6 mmHg (p = .005) lower in carriers versus noncarriers of the M235 allele in AA males only. Furthermore, the AGTR1 L191 allele showed a SBP lowering effect in subjects with a high socioeconomic status (SES;p = .048) and a DBP lowering effect in AAs (p = .038). Haplotype analyses identified a protective haplotype (C-521, 191L and A1166) for LVM levels (p = .03). LVM in individuals homozygous for this haplotype was 12.9 g lower than those homozygous for the most common haplotype (-521T, 191L and A1166). No significant interactions were found between the AGT M235T polymorphism and any of the single SNPs or haplotypes of the AGTR1 gene. Our results in multiethnic youth uncover an ethnicity and gender-specific effect of the AGT M235T polymorphism and a SES or ethnicity-specific effect of the AGTR1 L191L polymorphism on the progression of hypertension risk. A protective AGTR1 haplotype for LVM was also identified.
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PMID:Effects of angiotensinogen and angiotensin II type I receptor genes on blood pressure and left ventricular mass trajectories in multiethnic youth. 1679 Jan 49

The angiotensin II type 1 receptor (AGTR1) is the main target through which angiotensin II influences cardiovascular tone, cell growth, and fluid and electrolyte balance. AGTR1 polymorphism has been reported to associate with hypertension, myocardial infarction (MI), and metabolic traits. Here we describe a novel approach to quantitation of transcript haplotypes (QTH) of AGTR1. To determine relative allelic expression from haplotypes, within-individual-between-allele ratiometric analyses in placental cDNA were developed for the transcribed SNPs rs5182:C>T (encoding p.L191) and rs5186:A>C (3'-noncoding "A1166C"). Additionally, between-individual comparisons were made using TaqMan assays applied to both homozygous and heterozygous genotypes and haplotypes. In conjunction, linkage disequilibrium (LD) and genomic haplotype associations with metabolic syndrome were examined. There was no significant difference of mRNA level for alleles of rs5182:C>T, but allele and mRNA haplotypes carrying 1166C exhibited reduced abundance. The effect was much greater in CC homozygotes than in heterozygotes. The promoter region was confirmed to be in a separate haplotype block from the AGTR1 3' region containing rs5182:C>T and rs5186:A>C. Metabolic syndrome trait associations were strongest for the 3' block generally and for the C allele of rs5186:A>C specifically. All effects were much more prominent in homozygotes, possibly reflecting interallelic interaction through feedback loops of mRNA regulation. Differential abundance of AGTR1 mRNA haplotypes may mediate clinical phenotypic observations of the AGTR1 genotype.
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PMID:Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits. 1721 57

New methods are required for more objective estimation of the polymorphic genes contribution in multifactorial diseases. We suggest new approach based on the calculation of relative "score" as a sum of relevant genetic polymorphisms studied. Application of suggested approach is evaluated in analysis of the genes REN (19-83G>A), AGT (M235T), ACE (I/D), AGTR1 (1166A>C), AGTR2 (3123C>A), BKR2 (-58T>C and I/D) in children with arterial hypertension. The method proved that polymorphism of renin-angiotensin and kinin-bradikynin gene systems renders essential influence on formation of stably raised arterial pressure in girls.
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PMID:[Renin-angiotensin and kinin-bradykinin genes polymorphism effects on permanent arterial hypertension in children]. 1738 Aug 87

Animal microRNAs (miRNAs) regulate gene expression through base pairing to their targets within the 3' untranslated region (UTR) of protein-coding genes. Single-nucleotide polymorphisms (SNPs) located within such target sites can affect miRNA regulation. We mapped annotated SNPs onto a collection of experimentally supported human miRNA targets. Of the 143 experimentally supported human target sites, 9 contain 12 SNPs. We further experimentally investigated one of these target sites for hsa-miR-155, within the 3' UTR of the human AGTR1 gene that contains SNP rs5186. Using reporter silencing assays, we show that hsa-miR-155 down-regulates the expression of only the 1166A, and not the 1166C, allele of rs5186. Remarkably, the 1166C allele has been associated with hypertension in many studies. Thus, the 1166C allele may be functionally associated with hypertension by abrogating regulation by hsa-miR-155, thereby elevating AGTR1 levels. Since hsa-miR-155 is on chromosome 21, we hypothesize that the observed lower blood pressure in trisomy 21 is partially caused by the overexpression of hsa-miR-155 leading to allele-specific underexpression of AGTR1. Indeed, we have shown in fibroblasts from monozygotic twins discordant for trisomy 21 that levels of AGTR1 protein are lower in trisomy 21.
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PMID:Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3' untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes. 1766 90

The angiotensin II type 1 receptor (AGTR1) plays an integral role in blood pressure control, and is implicated in the pathogenesis of hypertension. Polymorphisms within this gene have been extensively studied in association with hypertension; however, findings are conflicting. To clarify these data, we conducted a systematic review of association studies of AGTR1 polymorphisms and hypertension, and performed a meta-analysis of the rs5186 variant. Results show that the currently available literature is too heterogeneous to draw meaningful conclusions. The definition of hypertension and gender composition of individual studies helps to explain this heterogeneity. Although the structure and splicing pattern of AGTR1 would suggest a likely effect of polymorphisms within the promoter region on gene function, few studies have been conducted thus far. In conclusion, there is insufficient evidence that polymorphisms in the AGTR1 gene are risk factors for hypertension. However, most studies are inadequately powered, and larger well-designed studies of haplotypes are warranted.
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PMID:Angiotensin II type 1 receptor polymorphisms and susceptibility to hypertension: a HuGE review. 1864 12

This longitudinal study examined the relationship between 2-year change in white matter hyperintense lesion (WML) volume and polymorphisms in genes coding for the angiotensin-II type 1 and type 2 receptors, AGTR1 A1166C and AGTR2 C3123A, respectively. 137 depressed and 94 non-depressed participants aged >or=60 years were enrolled. Standard clinical evaluations were performed on all participants and blood samples obtained for genotyping. 1.5-T MRI (magnetic resonance imaging) data were obtained at baseline and approximately 2 years later. These scans were processed using a semi-automated segmentation process, which allowed for the calculation of WML volume at each time point. Statistical models were tested for the relationship between change in WML volume and genotype, while also controlling for age, sex, diagnostic strata, baseline WML volume and comorbid cerebrovascular risk factors. In men, AGTR1 1166A allele homozygotes exhibited significantly less change in WML volume than 1166C carriers. We also found that men reporting hypertension (HTN) with the AGTR2 3123C allele exhibit less change in WML volume than hypertensive men with the 3123A allele, or men without HTN. There were no significant relationships between these polymorphisms and change in WML volume in women. No significant gene-gene or gene-depression interactions were observed. Our results parallel earlier observed gender differences of the relationship between other renin-angiotensin system polymorphisms and HTN. Further work is needed to determine whether these observed relationships are secondary to polymorphisms affecting response to antihypertensive medication, and whether antihypertensive medications can slow WML progression and lower the risk of morbidity associated with WMLs.
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PMID:Angiotensin receptor gene polymorphisms and 2-year change in hyperintense lesion volume in men. 1927 51

Multiple factors underlie susceptibility to essential hypertension, including a significant genetic and ethnic component, and environmental effects. Blood pressure response of hypertensive individuals to salt is heterogeneous, but salt sensitivity appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select and prioritize candidate aetiological genes for salt-sensitive hypertension. Additionally, we have compared allele frequencies and copy number variation for single nucleotide polymorphisms in candidate genes between indigenous Southern African and Caucasian populations, with the aim of identifying candidate genes with significant variability between the population groups: identifying genetic variability between population groups can exploit ethnic differences in disease prevalence to aid with prioritisation of good candidate genes. Our top-ranking candidate genes include parathyroid hormone precursor (PTH) and type-1 angiotensin II receptor (AGTR1). We propose that the candidate genes identified in this study warrant further investigation as potential aetiological genes for salt-sensitive hypertension.
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PMID:Computational analysis of candidate disease genes and variants for salt-sensitive hypertension in indigenous Southern Africans. 2088

AIMS. Blood pressure control is influenced by various genetic and environmental factors, and genetic susceptibility is important in the development of essential hypertension. Because the renin-angiotensin-aldosterone system (RAAS) has a key role in vasoconstriction, vasodilation, and sodium and electrolyte balance, it is central in blood pressure control and so is an appropriate target in hypertension treatments. The present study assessed the association of RAAS-related genes with blood pressure and hypertension in a Korean population. Single nucleotide polymorphisms (SNPs, n = 114) in nine RAAS-related genes (AGT, REN, ACE, ACE2, AGTR1, CYP11B2, NR3C2, MAS1, and CMA1) were assessed for their correlation with blood pressure and hypertension using genotype data of 8842 individuals from the Korea Association Resource subject pool. MAJOR FINDINGS. Linear regression analysis revealed a statistically significant association with blood pressure of 10 SNPs in six genes (ACE, ACE2, CYP11B2, NR3C2, MAS1, and CMA1). An additional hypertension case-control study identified 10 SNPs in NR3C2 and ACE that were linked to hypertension. PRINCIPAL CONCLUSION. Three SNPs (rs11737660, rs6810951, and rs10519963) in NR3C2 correlate with both blood pressure and hypertension. Genetic polymorphisms in RAAS-related genes appear to be associated with hypertension in a Korean population.
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PMID:Association between renin-angiotensin-aldosterone system-related genes and blood pressure in a Korean population. 2134 26

The objective of the study was to evaluate oxidative stress (OS) status in subjects with different cardiovascular risk factors. With this in mind, we have studied three models of high cardiovascular risk: hypertension (HT) with and without metabolic syndrome, familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) with and without insulin resistance. Oxidative stress markers (oxidized/reduced glutathione ratio, 8-oxo-deoxyguanosine and malondialdehide) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) and activation of both pro-oxidant enzyme (NAPDH oxidase components) and AGTR1 genes, as well as antioxidant enzyme genes (CuZn-SOD, CAT, GPX1, GSR, GSS and TXN) were measured in mononuclear cells of controls (n = 20) and patients (n = 90) by assessing mRNA levels. Activity of some of these antioxidant enzymes was also tested. An increase in OS and pro-oxidant gene mRNA values was observed in patients compared to controls. The hypertensive group showed not only the highest OS values, but also the highest pro-oxidant activation compared to those observed in the other groups. In addition, in HT a significantly reduced antioxidant activity and mRNA induction of antioxidant genes were found when compared to controls and the other groups. In FH and FCH, the activation of pro-oxidant enzymes was also higher and antioxidant ones lower than in the control group, although it did not reach the values obtained in hypertensives. The thioredoxin system was more activated in patients as compared to controls, and the highest levels were in hypertensives. The increased oxidative status in the presence of cardiovascular risk factors is a consequence of both the activation of pro-oxidant mechanisms and the reduction of the antioxidant ones. The altered response of the main cytoplasmic antioxidant systems largely contributes to OS despite the apparent attempt of the thioredoxin system to control it.
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PMID:Different impacts of cardiovascular risk factors on oxidative stress. 2201 50


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