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)

Prostacyclin inhibits platelet aggregation, smooth muscle cell proliferation, and vasoconstriction. The prostacyclin synthase (PGIS) gene is a candidate gene for cardiovascular disease. The purpose of this study was to locate possible mutations in the PGIS gene related to hypertension and cerebral infarction. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we discovered a T to C transition at the +2 position of the splicing donor site of intron 9 in patients with essential hypertension (EH). In vitro expression analysis of an allelic minigene consisting of exons 8-10 revealed that the nucleotide transition causes skipping of exon 9. This in turn alters the translational reading frame of exon 10 and introduces a premature stop codon (TGA). A three-dimensional model shows that the splice site mutation produces a truncated protein with a deletion in the heme-binding region. This splice site mutation was found in only one subject in 200 EH patients and 200 healthy controls. Analysis of the patient's family members revealed the mutation in two of the three siblings. The urinary excretion of prostacyclin metabolites in subjects with the mutation was significantly decreased. All subjects displaying the splice site mutation in the PGIS gene were hypertensive. In this study, we report a novel splicing mutation in the PGIS gene, which is associated with hypertension in a family. It is thought that this mechanism may involve in the pathophysiology of their hypertension.
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PMID:Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension. 1237 4

Previously, we discovered 3 polymorphisms in the prostacyclin synthase (PGIS) gene: 1) T-192G, in the 5-flanking region, a novel single-nucleotide polymorphism (SNP) that is not associated with essential hypertension (EH); 2) a variable number of tandem repeat (VNTR) polymorphism, 6 nucleotides upstream from the ATG start codon, that is associated with risk of cerebral infarction; and 3) C1117A, in exon 8, an SNP that does not cause an amino acid change in codon 373, and that is associated with risk of myocardial infarction (MI). The purpose of the present study was to establish haplotypes of the PGIS gene consisting of these 3 polymorphisms, and to assess the association between these haplotypes and EH. We detected 19 haplotypes. There was no significant difference in the overall distribution of haplotypes between EH and normotensive subjects. To summarize, we successfully identified haplotypes of the PGIS gene, and these haplotypes were not associated with EH.
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PMID:Haplotype analysis of the prostacyclin synthase gene and essential hypertension. 1292 23

Nitric oxide(NO), a potent vasodilator produced by endothelial cells, plays an important role in the regulation of blood pressure and regional blood flow, and also inhibits platelet aggregation and leukocyte adhesion to vascular endothelium and inhibits vascular smooth muscle cell proliferation. Various genetic polymorphisms of the endothelial nitric oxide synthase(eNOS) gene have been reported as susceptibility genes in a number of cardiovascular diseases. The functional significance of these polymorphisms has not yet been demonstrated, but recent study revealed that eNOS Glu298Asp variant is likely to have a functional effect on the eNOS protein. The missense Glu298Asp variant was correlated with increased coronary spasm, myocardial infarction, essential hypertension, left ventricular hypertrophy, carotid atherosclerosis, and cerebral infarction.
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PMID:[NOS gene polymorphism]. 1473 42

Malignant hypertension is a rare but serious syndrome complicating 1% of essential hypertension and causing neurological, renal and cardiac complications. Despite improved anti-hypertensive medication, the incidence of this condition fails to decline. In the first part of this review, we discuss transgenic rat models of malignant hypertension, generated by over-expressing renin, to illustrate the role of the renin-angiotensin system in the development of systemic hypertensive vascular remodelling and hypertension. In the second part, we focus on the cerebrovascular response to hypertension and discuss new data using a conditional, transgenic model of malignant hypertension, the inducible hypertensive rat (IHR). Cerebral infarction associates strongly with hypertension in man and the mechanisms by which hypertension predisposes to different types of stroke remains poorly understood. Rats have similar cerebrovascular anatomy and structure to humans and as such provide a good experimental tool. To date, such models lack controllability and blood-pressure matched controls. Using the IHR, we have manipulated dietary salt and water intake to generate a novel, controllable stroke phenotype. Hypertensive small-vessel stroke develops over a predictable time period, permitting the study of developing cerebrovascular lesions. Systemic end-organ injury and hypertension are not affected. Dissociation of the systemic and central vascular responses in this way, will allow for comparative study of animals with equivalent hypertension, genetic background and systemic features of hypertension with or without stroke.
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PMID:The role of the renin-angiotensin system in malignant vascular injury affecting the systemic and cerebral circulations. 1476 41

TH01 is a tetrameric short tandem repeat locus located in intron 01 of the tyrosine hydroxylase gene. The tyrosine hydroxylase catalyzes the hydroxylation of L-tyrosine to L-DOPA and is the rate limiting enzyme in the synthesis of catecholamines like noradrenaline or adrenaline, which are pivotal in the regulation of blood pressure. In a clinical study a strong correlation between alleles *9.3 and *10 and essential hypertension was observed ([2] Hypertension 32: 676-682). To further investigate this association, we typed TH01 in 296 autopsy cases and correlated the genotypes to the heart weight as parameter for myocardial hypertrophy. No significant correlation was observed. Moreover, dividing the studied cases into 2 groups, one including 172 casualties from hypertension-associated diseases (myocardial infarction, left heart failure, aortic aneurysm, spontaneous intracerebral bleeding and cerebral infarction) and one consisting of 124 cases of death unrelated to hypertension, revealed similar allelic frequencies for both groups. Our data thus suggest that TH01 long alleles appear not to lead to a significant increase in the incidence of myocardial hypertrophy or other hypertension associated diseases. This could be explained by a relatively small impact of the TH01 genotype on the blood pressure or by counteraction of another mechanism related to catecholamines and their effect on the human body.
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PMID:TH01, a tetrameric short tandem repeat locus in the tyrosine hydroxylase gene: association with myocardial hypertrophy and death from myocardial infarction? 1573 19

Prostacyclin (PGI2) inhibits platelet aggregation and vasoconstriction. Prostacyclin synthase (PGIS), a catalyst of PGI2 synthesis from prostaglandin H2, is widely distributed and predominantly found in vascular endothelial and smooth muscle cells. The PGIS gene is localized to 20q13.11-13, and a candidate gene for cardiovascular disease. We discovered mutations and polymorphisms in this gene and reported that they were associated with essential hypertension, myocardial infarction and cerebral infarction. These results suggest that PGI2 function depends on the different alleles of the PGIS gene and that they may influence the risk of cardiovascular diseases. Thus, individualized management strategies, such as administration of PGI2 analog, could be selected for variants of this gene to help prevent the development of cardiovascular diseases.
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PMID:Prostacyclin synthase gene: genetic polymorphisms and prevention of some cardiovascular diseases. 1585 2

Elevated serum uric acid (UA) is frequently encountered in individuals with hypertension, but whether the relationship between UA and cardiovascular events is circumstantial or causal remains to be answered. We examined the association between serum UA and left ventricular mass index (LVMI) and investigated prospectively whether the combination of UA and LVMI can predict the incidence of cardiovascular disease (CVD) in asymptomatic subjects with essential hypertension. A total of 619 subjects (mean age, 61 years; 52% female) free of prior CVD were included in this study. A significant association between UA and LVMI was also confirmed in multiple regression analysis (male: F=4.29, P<0.04; female: F=4.24, P<0.05). During follow-up (mean, 34 months), 28 subjects (14 female) developed CVD including myocardial infarction, angina pectoris, congestive heart failure, cerebral infarction, and transient cerebral ischemia. Sex-specific median values were used to separate the higher group from the lower group of UA and LVMI. Kaplan-Meier curves showed a significantly poorer survival rate in the group with higher UA and LVMI (LVMI, male: >126.9, female: >112.0 g/m2; UA, male: >374.7, female: >303.3 micromol/L; log-rank chi2=13.18; P<0.01). Multivariate Cox regression analysis showed that the combination of higher UA and LVMI was an independent predictor for CVD events (hazard ratio, 2.38; P<0.03). Our findings demonstrate that UA is independently associated with LVMI and suggest that the combination of hyperuricemia combined with left ventricular hypertrophy is an independent and powerful predictor for CVD. The association between UA and CVD events may be introduced in part because of a direct association of UA with LVMI.
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PMID:Uric acid, left ventricular mass index, and risk of cardiovascular disease in essential hypertension. 1638 May 20

The present review examines various reports describing prevalence of primary aldosteronism (PA) among hypertensives and the screening method of PA to better understand the current concepts used for diagnosing and managing PA among clinicians as well as specialists. Here, we describe and compare the prevalence of PA in Japan, which is well known to induce various vascular complications due to hyperaldosteronemia, resulting in cerebral infarction, myocardial infarction and renal failure, with that in another Asian area, US, European countries, Australia and Africa. The incidence rates for PA among hypertensives were recently reported to be widely raged between 3.2% and 20%. Those discrepancies are due in part to the completely different characteristics of the starting subjects used for studying the prevalence. Moreover, the criteria for screening PA among hypertensives, including aldosterone-renin ratio (ARR), and confirmatory tests for definitely diagnosing PA, such as saline infusion test are varied. We had already reported that a diagnosis of PA was made in 61 (6%) of the 1,020 hypertensive patients during the past five years, from 1995 until 1999. In our study, only 18% of the patients showed a serum K level of 3.3 mEq/l or less. Thus, many clinicians seem to misdiagnose PA as essential hypertension, because of absence of hypokalemia. Finally, we describe highlight key evidence for optimal methods for screening and definitely diagnosing PA among hypertensive patients in order to avoid misjudgment before or after treating hypertensive patients.
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PMID:Prevalence of primary aldosteronism: should we screen for primary aldosteronism before treating hypertensive patients with medication? 1712 64

Diagnosis of essential hypertension is created per exclusionem--with exclusion of all, so called secondary hypertensions (nephrogenic, endocrine conditioned etc). Idea and the name-essential hypertension are unclear. We have a lot of hypotheses about mechanisms of hypertension but no one is explaining satisfactorily the "fixation" of hypertension. From this point of view essential hypertension looks more like a syndrome than disease sui generis. Authors analyzed all possible pathways of hypertension origin as well as compensatory mechanisms in peripheral circulation in effort to reach relevant tissue perfusion. If these mechanisms lead to salt and water retention the best mode of the treatment would be to influence volume and blood vessels lumen. It is clear that optimization of blood pressure is advantageous for prevention of vascular catastrophes (myocardial and cerebral infarction). Nevertheless inadequate lowering of the peripheral tissue perfusion (kidney, CNS) can lead to degenerative changes in tissues and to disturbances in centrally regulated processes of blood pressure.
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PMID:[Essential hypertension--syndrome, or compensatory mechanism]. 1832 38

Prostacyclin (PGI2) inhibits platelet aggregation and vasoconstriction. PGI2 synthase (PTGIS), a catalyst of PGI2 synthesis from prostaglandin H2, is widely distributed and predominantly found in vascular endothelial and smooth muscle cells. The PTGIS gene is localized to 20q13.11-13 and a candidate gene for cardiovascular disease. We discovered mutations and polymorphisms in this gene and reported that they were associated with essential hypertension, myocardial infarction, and cerebral infarction. These results suggest that PGI2 function depends on the different alleles of the PTGIS gene and that they may influence the risk of cardiovascular disease. Thus, individualized management strategies, such as the administration of PGI2 analogues, could be selected for variants of this gene, to help prevent the development of cardiovascular disease.
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PMID:Genetic polymorphisms of prostacyclin synthase gene and cardiovascular disease. 2035 47


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