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

The aldosterone synthase gene (CYP11B2) is an important candidate gene region in essential hypertension. We therefore studied the association of -344T/C polymorphism of the CYP11B2 gene with the presence and severity of hypertension in a case-control study. We studied 369 individuals, of whom 213 were hypertensive patients (139 controlled hypertensive, 74 resistant hypertensive) and 156 were healthy normotensive subjects. The -344T/C polymorphism of the CYP11B2 gene was determined using polymerase chain reaction - restriction fragment length polymorphism analysis. The distribution of genotypes in normotensive controls and hypertensive subjects were: TT 25.6 vs. 31.9 %, TC 51.9 vs. 57.3 % and CC 22.4 vs. 10.8 %. The -344T/C variant was associated with hypertension. Subjects carrying the -344T allele had a greater risk of hypertension compared to those having C allele (chi(2)=5.89, p<0.05). The frequency of CC genotype was significantly lower in hypertensive patients than in normotensive controls (chi(2)=9.44, p<0.01). A stepwise logistic regression analysis confirmed these findings. We did not find an association of -344T/C variant with the resistance of hypertensive patients to combination therapy, but we observed an association of -344T/C polymorphism of aldosterone synthase gene with increased risk of hypertension. These results support a potential role of -344T/C CYP11B2 gene polymorphism in genetic predisposition to develop hypertension.
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PMID:Association of the -344T/C aldosterone synthase gene variant with essential hypertension. 1909 39

Aldosterone is a key regulator of electrolyte and water homeostasis and plays a central role in blood pressure regulation. Hormonal changes during pregnancy, among them increased progesterone and aldosterone production, lead to the required plasma volume expansion of the maternal body as an accommodation mechanism for fetus growth. This review discusses the regulation of aldosterone production by aldosterone synthase (CYP11B2); the impact on aldosterone secretion due to the presence of a chimeric gene originating from a crossover between CYP11B1 and CYP11B2 in glucocorticoid remediable aldosteronism (GRA) - the inherited form of hypertension; enhanced aldosterone production in aldosterone-producing adenoma (APA); and idiopathic hyperaldosteronism (IHA). Features of hyperaldosteronism are also found in patients with apparent mineralocorticoid excess (AME), in which glucocorticoids exacerbate activation of the mineralocorticoid receptor (MR) because of a defect in the 11beta-hydroxysteroid dehydrogenase type 2 enzyme. Regulation of aldosterone production and tissue-specific activation of the mineralocorticoid receptor are prerequisites for optimal control of body fluids and blood pressure during pregnancy and contribute largely to the wellbeing of the mother-to-be.
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PMID:Hyperaldosteronism in pregnancy. 1917 90

With the aim to investigate association of polymorphisms of candidate genes with clinical peculiarities of hypertensive disease in patients having burdened familial anamnesis we examined 413 (229 men and 184 women, mean age 60.3 +/- 0.59 years) patients with essential arterial hypertension (AH). Determination of alleles and genotypes of polymorphic markers of ACE, AGT, AT2R1, CYP11B2, NOS3, ENDl, GNB3, PPARA, PPARG2, MTHFR, CAT, SOD2, PON1, PON2 sigma APOB, APOE, LPL genes was carried out with the use of polymerase chain reaction. Patient with AH having hereditary load were younger (58.9 +/- 0.75 and 61.3 +/- 0.89 years, respectively, p=0.017) and had significantly lower age of debut of the disease (44.4 +/- 0.84 and 47.5 +/- 1.03 years, respectively; p=0.013), higher values of systolic (204.8 +/- 7.66 and 187.0 +/- 2.04 mm Hg; p=0.032) and diastolic (111.2 +/- 1.05 and 107.3 +/- 1.17 mm Hg, respectively; p=0.025) arterial pressure (AP) compared with patients with AH without hereditary loaded anamnesis. Portion of patients with 3 degree of severity of AH was higher among patients with "familial" AH (53.6 and 44.1%, respectively, p=0.018). Early debut (in the age younger than 45 years in men and 55 years in women) was associated with carriage of genotype TT of polymorphic marker C825 of GNB3 gene (OR 2.65 95CI [1.27-5.54], p=0.005) and genotype AA of polymorphic marker A(A153)G of AT2R1 gene (OR 1.67 95% CI [1.03-2.77], p=0.024). Higher AP level corresponding to 3-rd degree AH in the group of patients with burdened familial anamnesis was associated with carriage of Asn allele of polymorphic marker Lysl98Asn of EDN1 gene (OR 2.24 95% CI [1.20-4.18], p=0.008), 4a allele of polymorphic marker 4a/4b of NOS3 gene (OR 2.23 C/[1.29-3.83], p=0.002), genotype ArgArg of polymorphic marker Glnl92Arg of PON1 gene (OR 6.14 C7[1.46-25.67], p=0.01), T allele of polymorphic marker of C825T gene GNB3 (OR 1.75 C/[1.11-2.76], p=0.01) and genotype AA of polymorphic marker A(A153)G of AT2R1 gene (OR 2.61 C/11.29-5.34], p=0.005). In patients without burdened familial anamnesis 3-rd degree AH was associated with higher frequency of allele Ala of polymorphic marker Pro12A1a of PPARG2 gene.
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PMID:[Association of genetic factors with clinical peculiarities of hypertensive disease in patients with burdened familial anamnesis]. 1925 15

Animal models suggest that explanations for the association of low birthweight with adult hypertension may include chronic activation of the hypothalamic-pituitary-adrenal or renin-angiotensin-aldosterone axes. In humans, low birthweight predicts elevated plasma cortisol, but associations with aldosterone have not been reported. We measured aldosterone in serum samples from 205 men and 106 women from 67 to 78 years of age, from Hertfordshire, UK, for whom birthweight was recorded. Participants underwent an overnight low-dose (0.25 mg) dexamethasone suppression test and a low-dose (1 mug) ACTH (corticotropin) stimulation test and were genotyped for the -344 C/T polymorphism of the CYP11B2 gene encoding aldosterone synthase. Median aldosterone was 6.22 ng/dL (range 0.15 to 38.74) and was higher in men than women (P<0.0001). Higher aldosterone levels after both dexamethasone and ACTH stimulation were associated with higher blood pressure (r=0.20, P=0.001; r=0.33, P<0.0001, respectively) and with lower birthweight (r=-0.16, P=0.008; r=-0.21, P=0.001, respectively). These associations remained significant after adjusting for age, gender, obesity, and genotype. Our findings supplement previous evidence that aldosterone is an important regulator of blood pressure and suggest that factors in early life that retard fetal growth and program activation of the hypothalamic-pituitary-adrenal axis in humans result not only in higher glucocorticoid activity but also in increased mineralocorticoid activity.
Hypertension 2009 Jun
PMID:Programming of hypertension: associations of plasma aldosterone in adult men and women with birthweight, cortisol, and blood pressure. 1938 Jun 12

A thymidine-to-cytosine substitution in the -344 promoter region of the aldosterone synthase gene (CYP11B2) has been associated with essential hypertension in some but not all studies conducted in Chinese. We performed a meta-analysis to evaluate the association of the -344C/T polymorphism with essential hypertension in Chinese. A total of 7,472 individuals (4,259 unselected hypertensive patients and 3,213 normotensive controls) from 9 case-control studies were included in the present investigation. Significant associations between the risk of hypertension and the CC genotype and C allele frequencies were found in a total of 19 studies. Our findings support the notion that the CYP11B2 -344C/T polymorphism is associated with essential hypertension. In addition, C allele frequency was found to be lower in southern Chinese controls than in their northern counterparts, and the higher TT genotype homozygous frequency in the southern Chinese supports the hypothesis that the northern Chinese are of southern origin.
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PMID:Association between aldosterone synthase CYP11B2 polymorphism and essential hypertension in Chinese: a meta-analysis. 1940 59

Excessive production of aldosterone has been implicated in the pathogenesis of hypertension and heart failure. One approach to ameliorate the deleterious effects of aldosterone is to suppress its biosynthesis. The enzyme aldosterone synthase (CYP11B2) is responsible for the final step of aldosterone synthesis. It requires electron transfer from the adrenodoxin/adrenodoxin reductase system to catalyze the production of aldosterone. A stable cell line simultaneously overexpressing recombinant human CYP11B2 as well as human adrenodoxin and adrenodoxin reductase was established to help maximize the enzyme activity. The homogenate of these cells was used to develop an in vitro CYP11B2 assay using 11-deoxycorticosterone as a substrate. By the same strategy, another stable cell line simultaneously overexpressing human 11beta-hydroxylase (CYP11B1), an enzyme responsible for the final step of cortisol biosynthesis, and the two electron transfer proteins was also established, and an in vitro CYP11B1 assay using 11-deoxycortisol as a substrate was likewise developed to assess the selectivity of CYP11B2 inhibitors. FAD286, a reference CYP11B2 inhibitor, inhibited CYP11B2 and CYP11B1 activities with IC(50) values of 1.6+/-0.1 and 9.9+/-0.9 nM (mean+/-SEM, n=3-6), respectively. Kinetics studies revealed that the compound inhibited the activity of both enzymes competitively with respective K(i) values of 0.8+/-0.04 and 2.2+/-0.2 nM (n=3-4). These assays can be used for assessing the potency and selectivity of CYP11B2 inhibitors for the treatment of hypertension and heart failure.
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PMID:Coexpression of CYP11B2 or CYP11B1 with adrenodoxin and adrenodoxin reductase for assessing the potency and selectivity of aldosterone synthase inhibitors. 1962 40

Hyperaldosteronism is associated with elevated cardiovascular risk. Using mineralocorticoid receptor antagonists a significant reduction in mortality was archived in patients with heart failure. In addition, in refractory hypertension and in patients with metabolic syndrome aldosterone seems to play an important role. Therapy with mineralocorticoidreceptor (MR) antagonists is feasible when aldosterone levels are elevated, in particular in patients with aldosterone-escape. Of particular interest is primary aldosteronism (PA). PA is one of the major causes of secondary hypertension. Since most patients with PA present with normokalemia screening has to be performed using the aldosterone renin ratio, in particular patients with refractory hypertension, young hypertensive patients and patients with incidentaloma. One has to point out that drugs that interfere with the aldosterone-renin-aldosterone-system need to be discontinued or changed. After successful screening, confirmatory testing (e.g. i.v. salt suppression test) has to follow. In order to differentiate between unilateral and bilateral disease computed tomography and adrenal vein sampling are performed. While unilateral adenomas can be cured surgically, bilateral adrenal hyperplasia is treated with MR-antagonists. In case of positive family history for PA one should consider familiar hyperaldosteronism (FH). Three forms are currently defined--FH type I, type II and type III. A hybrid gene consisting of CYP11B1 and CYP11B2 that produces aldosterone in an ACTH dependant manner can be found in FH type I. Diagnosis is verified by long range PCR. No underlying monogenetic cause for FH II and FH II could be detected so far. Through mechanisms way more than water and salt regulation, hyperaldosteronism can negatively influence cardiovascular mortality and morbidity and should therefore play an important part in diagnosis and therapy of arterial hypertension.
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PMID:[The role of aldosterone in hypertension]. 2021 71

The extent of genetic influence in the aetiology of gestational hypertension has not been completely determined. The aim of this study was to analyse the relationship between aldosterone levels and the -344T/C polymorphism of the aldosterone synthase gene (CYP11B2) and to investigate the frequency of the S810L mutation of mineralocorticoid receptor (MR) in gestational hypertension. One hundred women with pregnancy-induced hypertension and 100 with normal pregnancy were studied to measure serum aldosterone and progesterone levels and for the genotypification of the -344T/C polymorphism of CYP11B2 gene and the S810L mutation of MR by RFLP-PCR and SSP, respectively. Serum aldosterone levels were reduced (<0.000001) and serum progesterone levels increased (<0.000001) in gestational hypertensive women as compared with normal pregnant women. The -344T/C of CYP11B2 genotypic frequencies were similar in the hypertensive and normotensive pregnant women. The 810L-mutated allele of MR was found in 12% of the hypertensive and 9.4% of the normotensive pregnant women. In contrast to the observations made in preeclampsia, the genotype of -344T/C of CYP11B2 was neither related with gestational hypertension nor with aldosterone levels at delivery. The frequency of the S810L mutation was similar in the hypertensive and normotensive women but higher than observed in other reports.
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PMID:Relationship of aldosterone synthase gene (C-344T) and mineralocorticoid receptor (S810L) polymorphisms with gestational hypertension. 2053 41

Stroke is a complex disease caused by combination of multiple risk factors. Recent findings have suggested that stroke has a significant genetic component. Various types of genetic polymorphisms have been suggested to contribute to the risk of stroke. Gene polymorphisms of renin-angiontensin aldosterone system (RAAS) have been suggested to be risk factors for hypertension, cardiovascular diseases and stroke. In the present case-control study we investigated the association of -344C/T (rs1799998) [corrected] polymorphism in the promoter region of the human aldosterone (CYP11B2) gene with genetic predisposition to hypertension, ischemic stroke and stroke subtypes classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Four hundred and three stroke patients (hypertensives:normotensives=219:184) and three hundred and ninety four, sex and age matched healthy controls (hypertensives:normotensives=118:276) were involved in the study. The region of interest in the CYP11B2 gene was amplified by polymerase chain reaction and genotypes determined by subjecting the PCR products to restriction digestion by the enzyme HaeIII. Significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. TT genotype and T allele associated significantly with hypertension and stroke (p<0.000 in hypertension and p=0.000 in case of stroke). A stepwise logistic regression analysis confirmed these findings. To establish that this polymorphism is associated with stroke independent of hypertension, we compared stroke patients without hypertension with normotensive controls. Significant difference was observed in genotypic distribution and allelic frequency between the two groups (p=0.000). Further evaluating the association of this polymorphism with stroke subtypes we found significant associations with intracranial large artery atherosclerosis, lacunar stroke and cardioembolic stroke (p=0.000 in each case). In conclusion our study suggests that -344T allele of CYP11B2 gene is an important risk factor for hypertension and ischemic stroke. However, this is a preliminary study and the results need to be confirmed in a larger cohort.
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PMID:Association of the -344C/T aldosterone synthase (CYP11B2) gene variant with hypertension and stroke. 2059 12

Aldosterone, the final component of the renin-angiotensin-aldosterone system, plays an important role in the pathophysiology of hypertension and congestive heart failure. Aldosterone synthase (CYP11B2) catalyzes the last three steps of aldosterone biosynthesis, and as such appears to be a target for the treatment of these disorders. A sulfonamide-imidazole scaffold has proven to be a potent inhibitor of CYP11B2. Furthermore, this scaffold can achieve high levels of selectivity for CYP11B2 over CYP11B1, a key enzyme in the biosynthesis of cortisol.
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PMID:The discovery of potent inhibitors of aldosterone synthase that exhibit selectivity over 11-beta-hydroxylase. 2061 92


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