Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic disorders in the gene encoding P450c17 cause 17 alpha-hydroxylase deficiency. The consequent defects in the synthesis of cortisol and sex steroids cause sexual infantilism and a female phenotype in both genetic sexes as well as mineralocorticoid excess and hypertension. A 15-yr-old patient from Germany was seen for absent pubertal development and mild hypertension with hypokalemia, high concentrations of 17-deoxysteroids, and hypergonadotropic hypogonadism. Analysis of her P450c17 gene by polymerase chain reaction amplification and direct sequencing showed mutation of codon 440 from CGC (Arg) to CAC (His). Expression of a vector encoding this mutated form of P450c17 in transfected nonsteroidogenic COS-1 cells showed that the mutant P450c17 protein was produced, but it lacked both 17 alpha-hydroxylase and 17,20-lyase activities. To date, 15 different P450c17 mutations have been described in 23 patients with 17 alpha-hydroxylase deficiency, indicating that mutations in this gene are due to random events.
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PMID:Point mutation of Arg440 to His in cytochrome P450c17 causes severe 17 alpha-hydroxylase deficiency. 802 20

We evaluated 675 men and 190 women who had no symptoms or history of clinical CHD, to determine the prevalence and risk factor correlates of CAC deposits as a marker of atherosclerosis. Measurements were taken noninvasively by ultrafast CT. The presence and extent of CAC deposits as measured by ultrafast CT was determined in all subjects, who also received personal and family medical history and risk factor questionnaire. The prevalence of CAC deposits increased significantly with age, ranging from 15% and 30% in men and women, respectively, < 40 years of age to 93% and 75% in those aged > or = 70 years. Prevalence and total score also increased by the number of risk factors present, although in those aged > 60 years a high prevalence (> 80% in men) of calcium was present regardless of the presence of risk factors. In multiple logistic regression, age, male gender, hypertension, diabetes, hypercholesterolemia, and obesity were independently associated with CAC deposits. These results suggest a high prevalence of atherosclerosis with increasing age and the presence of risk factors in men and women who have no symptoms. Studies to determine the prognostic value of CAC in individuals with no symptoms are needed to determine which populations may benefit most from CAC deposit screening.
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PMID:Coronary calcium and atherosclerosis by ultrafast computed tomography in asymptomatic men and women: relation to age and risk factors. 829 11

Steroid 11 beta-hydroxylase is encoded by two homologous genes, CYP11B1 and CYP11B2, located on chromosome 8q21-22. CYP11B1 encodes a specific cytochrome P-450 (P-450c11) necessary for cortisol biosynthesis, with predominantly 11 beta-hydroxylase and moderate 18-hydroxylase activity, whereas CYP11B2 encodes another isozyme (P-450cmo) necessary for aldosterone biosynthesis, with 11 beta-hydroxylase, 18-hydroxylase and 18-oxidase activities (the latter two termed corticosterone methyl-oxidase I and II; CMO-I and II, respectively). Two steroid biosynthetic defects, both relatively frequent in Israel, are caused by specific mutations in each of these genes. 11 beta-Hydroxylase deficiency is frequent among Jews from Morocco (1 in 5000 to 7000 births), and is characterized by virilization, hypertension, impaired cortisol biosynthesis, and increased deoxycorticosterone and androgens. Affected individuals have a single base substitution in exon 8 of CYP11B1, codon 448, from CGC (arginine) to CAC (histidine). This sequence, normally absent in CYP11B2, constitutes a true point mutation within the heme binding domain of CYP11B1 that results in marked impairment of enzymatic activity. The clinical expression is characterized by a wide range of variability in the signs of both androgen and mineralocorticoid excess, even though an identical mutation was found in all but one of the affected alleles examined. CMO-II deficiency is frequent among Jews from Iran (1 in 4000 births), and is characterized by a typical salt-wasting syndrome, increased 18-hydroxycorticosterone, impaired aldosterone biosynthesis, and a high ratio of these steroids. No mutation was found in CYP11B1, but all individuals affected were homozygous for two missense mutations in CYP11B2. The first, in exon 3, codon 181, from CGG (arginine) to TGG (tryptophane) is a mutation that completely abolishes both CMO-I and II activities, whereas the second, in exon 7, codon 386, from GTG (valine) to GCG (alanine) is a more conservative substitution that produces only a minimal reduction in CMO-I activity. Individuals homozygous for either one of these mutations are asymptomatic.
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PMID:Mutations in human 11 beta-hydroxylase genes: 11 beta-hydroxylase deficiency in Jews of Morocco and corticosterone methyl-oxidase II deficiency in Jews of Iran. 848 57

Because evidence suggests that endothelin-1 (ET-1) plays a role in the pathogenesis of hypertension, we examined the variability within the ET-1 and the ET(A) receptor genes in patients with essential hypertension (EH). Genomic DNA was used for amplification of both genes by PCR. Polymorphisms within these genes were identified by single-strand conformation polymorphism (SSCP) analysis and subsequent DNA sequencing. Single-base insertions (C at position 121; A at position 138) were identified in the untranslated region of exon 1 of the ET-1 gene. The C insertion was invariant, whereas the A insertion, which abolished a BsiY1 restriction site, occurred only in samples that showed altered mobility profiles on SSCP analysis. This strategy also identified a silent polymorphism in codon 323 (CAC-->CAT) of the ET(A) receptor gene, which created an AflII restriction site. The frequency distribution of these polymorphisms was compared in an EH population [diastolic blood pressure (DBP) > or = 95 mm Hg; n = 100] and a matched normotensive (NT) group (BP < or = 140/85 mm Hg). No significant differences in AflII genotype distribution were found between the EH and NT groups. However, chi 2 analysis suggested a significant difference between the BsiY1+/+, BsiY1-/+, and BsiY1-/- genotype frequencies in the two groups (EH 58:38:4%; NT 47:44:9% (p = 0.045)). In addition, two-way analysis showed a strong correlation between DBP and the BsiY1-/- polymorphism. These results suggest that these polymorphisms act as markers for the level of DBP.
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PMID:Genetic variability of the ET-1 and the ETA receptor genes in essential hypertension. 858 78

The properties of normotensive and hypertensive rat lines were investigated by the DNA fingerprinting method using a multilocus micro-satellite (CAC)5 probe. The HaeIII and HinfI restriction endonucleases were found to be the most informative enzymes in this case. The high genetic homogeneity of the ISIAH line, a rat line with inherited stress-sensitive arterial hypertension created at the Institute of Cytology and Genetics, was demonstrated. The lack of intralinear polymorphism was also typical to Japanese SHR rats with spontaneous arterial hypertension. Normotensive WAG rats had identical fingerprinting patterns, while the relative intensity of some bands was different. The outbred normotensive Wistar line maintained at the Institute, appeared to carry 30% polymorphic alleles. Hypertensive lines differed from the normotensive by a number of genetic markers.
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PMID:[Characterization of rat lines with normotensive and hypertensive status using genomic fingerprinting]. 910 57

Apparent mineralocorticoid excess (AME) characterized by early-onset hypertension and hypokalemia is due to congenital deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). Two isoforms of human 11 beta HSD are known, and the type 2 isoform (11 beta HSD2) has been recently shown to be responsible for AME. In this study we have analyzed the 11 beta HSD2 gene of a Japanese patient with AME. PCR amplification and subsequent nucleotide sequencing of the 11 beta HSD2 gene from the patient and his family members revealed that the patient has a compound heterozygous mutation of this gene. In 1 allele, an undescribed single nucleotide transition in codon 208 in exon 3 resulted in a substitution of arginine to histidine (CGC to CAC: R208H). In the other allele, a deletion of 3 nucleotides in codons 337-338 in exon 5 resulted in a substitution of arginine to histidine and a deletion of tyrosine residue (CGCTAT to CAT: R337H, delta Y338), which has been previously shown to abolish 11 beta HSD2 enzyme activity. A chloramphenicol acetyltransferase assay-based expression study involving the mineralocorticoid receptor indicated that the novel R208H mutation eliminates the enzymatic activity of 11 beta HSD2. From the genetic analysis of 50 healthy subjects, the novel R208H mutation was unlikely to be due to polymorphism. Together, these results indicate that this patient is a compound heterozygote for the mutation in the 11 beta HSD2 gene (R208H and R337H, delta Y338) and that these mutations inactivate the 11 beta HSD2 function and give rise to clinically manifest AME.
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PMID:A new compound heterozygous mutation in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess. 939 12

Using the molecular scanning technique of single-stranded conformational polymorphism, we examined the exon 17 of the insulin receptor (INSR) gene in 44 subjects of 6 essential hypertensive pedigrees and 2 normotensive pedigrees. In addition the serum levels of glucose and insulin during an oral glucose tolerance test (OGTT); blood lipid, and plasma angiotension II and angiotensinogen were done on these pedigrees. Upon direct sequence analysis, 5 individuals were found a single nucleotide substitution at the codon 1058 (CAC-->CAT), which didn't change the amino acid sequence. Among the five individuals 4 of them were from the families with history of hypertension, only one was from normotensive pedigree. Compared with those without the mutation, the individuals with the mutation had a lower ratio of fasting blood glucose to fasting serum insulin level (P < 0.01) and an elevated plasma Ang II concentration. (There was no significant difference, P > 0.05, probably due to the mutant cases which we studied were small). Thus, we conjectured that the mutation in codon 1,058 of the INSR gene might be related with the insulin resistance in hypertensive patients and subjects with the positive hypertensive history.
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PMID:[The study of mutation in exon 17 of insulin receptor gene in essential hypertensive pedigrees]. 1045 99

A search for DNA markers of hereditary arterial hypertension in ISIAH rats was performed by means of contemporary molecular genetic approaches. The backcross rat population used for the analyses was derived from a cross of the Wistar x ISIAH F1 progeny with the Wistar rats. Hybridization of the HaeIII-digested DNA samples with the (CAC)5 microsatellite probe revealed cosegregation of the basal arterial pressure value with the 4.8-kb polymorphic DNA fragment. Examination of the DNA polymorphism by means of polymerase chain reaction with arbitrary primers showed an association of the 700-bp polymorphic DNA fragment with the increase of arterial blood pressure under conditions of emotional stress.
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PMID:[Analysis of polymorphic DNA markers cosegregation with arterial blood pressure in ISIAH hypertensive rats]. 1049 34

In the present study, we investigated whether measures of brachial artery reactivity were associated with the presence and extent of subclinical coronary atherosclerosis in asymptomatic adults. Electron beam computed tomography was employed to assess the presence and quantity of CAC (coronary artery calcium) in 441 participants (mean age, 61 years; 49% men) without prior history of CHD (coronary heart disease) or stroke, and CAC score was calculated using the method described by Agatston and co-workers [(1990) J. Am. Coll. Cardiol. 15, 827-832] High-resolution ultrasound was employed to measure BAD (brachial artery diameter), FMD (flow-mediated dilatation) and NMD (nitroglycerine-mediated dilatation). CAC score and FMD were log-transformed after adding 1 to reduce skewness. Multivariable logistic and linear regression models based on generalized estimating equations were used to assess whether BAD, FMD and NMD were each independently associated with the presence and quantity of CAC after adjustment for CHD risk factors and use of statin and hypertension medication. CAC was detectable in 64% of participants. After adjustment for age and sex, FMD was not correlated (r=-0.06; P=0.27), BAD was positively correlated (r=0.16; P=0.004) and NMD was inversely correlated in a borderline significant manner (r=-0.10; P=0.084) with log(CAC+1). In multivariable logistic regression analyses, FMD was not associated, whereas higher BAD (P=0.021) and lower NMD (P=0.030) were independently associated with the presence of CAC. In multivariable linear regression analyses, higher BAD (P=0.004) and lower NMD (P=0.016), but not FMD, were independently associated with log(CAC+1). We conclude that greater diameter of the brachial artery and lower vasodilator response to nitroglycerine, but not FMD, are associated with subclinical coronary atherosclerosis.
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PMID:Brachial artery diameter and vasodilator response to nitroglycerine, but not flow-mediated dilatation, are associated with the presence and quantity of coronary artery calcium in asymptomatic adults. 1698 2

Increased aortic stiffness, as measured by pulse wave velocity (PWV) and augmentation index (Aix), and vascular calcification have been associated with an unfavourable cardiovascular outcome in hemodialysis patients. However, the majority of data have been published in white patients and epidemiological data are discordant on the fate of patients of different races. In this cross sectional study we measured PWV and Aix by applanation tonometry and coronary artery and thoracic aorta calcium score (CAC and AoC) by electron beam tomography (EBT) in 81 Blacks and 61 Whites on maintenance hemodialysis. Vascular stiffness measurements and EBT scans were performed within a week of each other. There was no difference between races in age, systolic blood pressure or gender distribution. Blacks had a more frequent history of hypertension (100% versus 89%; P=0.002), lower prevalence of dyslipidemia (30% versus 66%; P<0.001), higher PTH levels (geometric mean 607 pg/ml versus 245 pg/ml; P=0.039), received calcium based phosphate binders less frequently (37% versus 60%, P=0.007) and calcium antagonists more frequently than Whites (54% versus 28%; P=0.003). Nonetheless, the unadjusted and risk adjusted PWV and Aix, as well as CAC and AoC were not statistically different between races. In this dialysis cohort there was no difference in markers of vasculopathy between black and white patients despite differences in baseline clinical characteristics. Epidemiological data from the general population indicate that Blacks have lower calcium scores and stiffer vessels than Whites. Some studies in the renal populations suggest a better and others a similar survival of Blacks and Whites on hemodialysis. Our findings raise the important question of the prognostic significance of markers of vasculopathy in patients of different races and with different risk profiles.
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PMID:Markers of vascular disease do not differ in black and white hemodialysis patients despite a different risk profile. 1752 8


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