Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Constitutively active nitric oxide synthases (NOS) are a unique class of NADPH-dependent, calcium/calmodulin-dependent enzymes that catalyze the conversion of L-arginine to nitric oxide and L-citrulline. However, little is known about the molecular similarities or differences between the two prototypical constitutive NOS enzymes, endothelial NOS (ECNOS) and brain NOS (bNOS). The aims of this study were to begin characterizing the gene structure and tissue distribution of messenger RNAs (mRNAs) for ECNOS and bNOS and to examine the immunological resemblance of the proteins by Western blotting. Full-length complementary DNAs (cDNAs) encoding bovine ECNOS and rat bNOS hybridized, under high stringency, to different-sized fragments of endonuclease-digested bovine, rat, and human genomic DNA. In addition, more than one fragment was detected with both cDNAs, suggesting that ECNOS and bNOS genes contained multiple introns. Tissue distribution of ECNOS mRNA (4.4 kb) and bNOS mRNA (9.5 kb) in the rat was detected by Northern blotting. Patterns among tissue extracts were strikingly different, with ECNOS mRNA being most abundant in aorta, heart, lung, kidney, adrenal gland, spinal cord, and urogenital tissues and bNOS mRNA most prominent in brain regions, intestine, stomach, spinal cord, adrenal gland, and aorta. Interestingly, ECNOS cDNA detected two equally abundant RNA transcripts (4.4 and 4.0 kb) in most brain regions tested, suggesting an alternative splicing of the ECNOS pre-mRNA. Western blotting, using an ECNOS monoclonal antibody, recognized ECNOS protein from native bovine endothelial cells, cultured bovine endothelial cells, and COS cells transfected with ECNOS cDNA but did not recognize purified bNOS.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Jun
PMID:Genomic analysis and expression patterns reveal distinct genes for endothelial and brain nitric oxide synthase. 768 5

Recently, evidence has been presented for genetic linkage between the angiotensinogen gene and primary hypertension in humans. In the present study we examined whether a similar linkage between blood pressure and the angiotensinogen gene locus can be demonstrated in a widely used animal model of primary hypertension, the stroke-prone spontaneously hypertensive rat (Heidelberg colony, SHRSPHD). In 115 F2 hybrids bred from SHRSPHD and a normotensive reference strain, the Wistar-KyotoHD (WKYHD) rat, systolic and diastolic blood pressures and heart rate were determined by indwelling arterial catheters in the presence and absence of dietary sodium loading. In addition, left and right ventricular heart weight was measured. Using a newly developed polymorphic marker assay for the angiotensinogen gene based on polymerase chain reaction amplification of an exon 2 fragment and subsequent restriction endonuclease digestion, we performed a cosegregation study in this cohort. No evidence for cosegregation between the angiotensinogen gene locus and blood pressure or any other phenotypic parameter assessed was found. Although the SHRSP serves as a valuable model of hypertension, our data emphasize that disease-relevant genetic loci in humans and rats cannot be assumed to coincide.
Hypertension 1994 Jun
PMID:Unlike human hypertension, blood pressure in a hereditary hypertensive rat strain shows no linkage to the angiotensinogen locus. 791 49

To examine the association between von Willebrand Factor (vWF) concentrations and features of the insulin resistance syndrome, 208 patients with Type 2 (non-insulin-dependent) diabetes (NIDDM) and 80 healthy controls were studied. A restriction fragment length polymorphism in exon 12 of the vWF gene, detected by Aat II endonuclease, was also examined. vWF concentrations were elevated in the patient group (patients 1.28 IU ml-1 vs controls 1.12 IU ml-1, p = 0.003). Genotype frequencies were in Hardy-Weinberg equilibrium and genotype did not relate to vWF levels: means (95% CI) were AA 1.29 (1.29-1.44) IU ml-1 n = 3; AG 1.28 (1.22-1.26) IU ml-1 n = 48; GG 1.29 (1.25-1.39) IU ml-1 n = 155. vWF correlated with age (r = 0.23 p < 0.0005), duration of diabetes (r = 0.23, p < 0.001), and fibrinogen (r = 0.22, p = 0.002) in the patient group, but was unrelated to blood lipids, HbA1C, body mass index, glucose, hypertension, and smoking. In a linear regression model, age and insulin remained as independent predictors of vWF levels, explaining 16% of inter-individual variance in the patient group. In conclusion, these findings show vWF concentrations are elevated in NIDDM and are weakly related to features of the insulin resistance syndrome. No relationship was demonstrated between the gene polymorphism studied and vWF concentrations in this group.
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PMID:Levels of von Willebrand factor, insulin resistance syndrome, and a common vWF gene polymorphism in non-insulin-dependent (type 2) diabetes mellitus. 886 46

RFLP in the hsp70 gene encoding a major heat shock protein was analyzed in rat strains with high and normal arterial blood pressure. Dimorphism in the sets of DNA fragments was revealed after hybridization of the hsp gene leader sequence with rat DNA digested with BamHI restriction endonuclease. Type I RFLP was represented by the fragments of 12,200, 6500, 41,000 and 1600 bp in size. Type II RFLP corresponded to the set that included the fragments of 12,200, 6500, 2900, 1600, and 1200 bp in size. Interstrain polymorphism was demonstrated for the fragments of 4100, 2900 and 1200 bp. Furthermore, analysis of different rat strains showed that the 2900- and 1200-bp fragments were linked and formed by cleavage of the 4100-bp fragment with restriction endonuclease. This polymorphism was probably caused by the point A-->T mutation occurring in the BamHI recognition site located in the leader sequence of the hsp70 gene at a distance of +35 bp from the coding sequence. Examination of interstrain RFLP in the hsp70 gene indicated that the presence of 2900-bp fragment was not associated with hypertensive status in all experimental models of inherited arterial hypertension. This confirms the assumption on genetic heterogeneity of this common disease.
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PMID:[Polymorphism of the gene of heat shock protein hsp70 in lines of rats with normal and hypertensive status]. 958 65

Transgenesis is proving to be a powerful technique in studying the molecular genetics of hypertension. The ability to target specific mutations resulting in either loss of function, by gene deletion, the insertion of reporter sequences, or the subtle change of function by nucleotide replacement, can facilitate the understanding of gene function and its role in the manifestation of diseases. However an inherent problem associated with transgenic studies is the lack of consistent expression observed between independent lines of animals which have integrated the same transgene, a phenomenon known as 'position effect'. Small transgenes are almost invariably subject to position effect due to the absence of essential regulatory elements required to maintain an open chromatin structure. This phenomenon may be overcome if larger transgenes, isolated using vectors such as yeast artifical chromosomes (YACs), bacterial artificial chromosomes (BACs) or P1-based vectors, are used. Studies using such transgenes have reported levels of expression which are consistent between lines and dependent upon the number of copies integrated. The introduction of modifications into these large genomic clones is not practical by traditional restriction endonuclease strategies and so is dependent upon in vivo recombination to maintain structural integrity. Here we demonstrate the modification of a 100 Kb P1 clone spanning the renin locus using the BAC targeting strategy described by Yang et al (Nat Biotechnol 1997; 15: 859-865).
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PMID:Manipulating large genomic clones via in vivo recombination in bacteria. 1061 75

With a view to evaluating the putative involvement of cytokine gene variants in human essential hypertension, we carried out an association (case-control) study on 174 unrelated nationals (81 hypertensives and 93 normotensives) from the Abu Dhabi Emirate (UAE), a genetically homogeneous population also characterised by the absence of traditional confounding factors such as alcohol consumption and smoking. To that end, we targeted our investigation to five candidate gene loci-transforming growth factor beta1 (TGF-beta1), interferon gamma (IFN-gamma), epidermal growth factor (EGF), interleukin-1 beta (IL-1beta) and tumour-necrosis factor (TNF-alpha) genes. We investigated the distribution of genotypes and alleles of the six following dimorphic variants: TGF-beta1(*)10(T>C) and TGF-beta1(*)25(G>C), located at codons 10 and 25, respectively, of TGF-beta1; T874A in intron 1 of IFN-gamma; G61A in exon 1 of EGF; TaqI dimorphism at +3962 (exon 5) of IL-1beta; and -308A>G in the promoter of TNF-alpha. These six bi-allelic markers were visualised by methods based on the techniques of amplification refractory mutation system-polymerase chain reaction (for TGF-beta1, IFN-gamma, EGF and TNF-alpha) and by polymerase chain reaction-TaqI restriction endonuclease analysis in the case of IL-1beta. In each of the two groups (normotensives and hypertensives), genotype frequencies of all six markers occurred in Hardy-Weinberg proportions. There were, however, no statistical differences in the allele and genotype frequencies of any of the six markers between the two groups of subjects: TGF-beta1(*)10C frequencies were 0.46 and 0.49 (chi(2)=0.61; 2 d.f.; P=0.74) and TGF-beta1(*)25C were 0.07 and 0.08 (chi(2)=0.61; 2 d.f.; P=0.74) amongst normotensives and hypertensives, respectively; p(IFN-gamma(*)A874) were 0.41 in normotensives versus 0.46 in hypertensives (chi(2)=3.07; 2 d.f.; P=0.22); p(EGF (*)G61) were 0.51 versus 0.58 (chi(2)=1.76; 2 d.f.; P=0.41); p[IL-1beta (*)TaqI(+)] were 0.43 versus 0.36 (chi(2)=2.08; 2 d.f.; P=0.35); and p(TNF-alpha(*)-308G) were 0.80 versus 0.85 (chi(2)=1.29; 2 d.f.; P=0.53). There was also no difference in distribution and frequencies of haplotypes constructed with combinations of TGF-beta1(*)10(T>C) and TGF-beta1(*)25(G>C) sites. However, although they do not reach statistical significance (which may be due to the relatively restricted number of subjects included in this study), the distribution differences (in normotensives and hypertensives) observed in the cases of EGF and TNF-alpha reflect trends that could be expected from a mechanistic explanation of the pathways that underlie the patho-physiology of hypertension.
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PMID:A study of five human cytokine genes in human essential hypertension. 1200 75

Several candidate genes, chosen from the renin- angiotensin system, were examined for their association with essential hypertension. The genes of the renin- angiotensin system (RAS) are good candidates for such an approach because this system is well known to be involved in the control of blood pressure. One of these candidate genes is the gene encoding for angiotensinogen (the most important gene of the RAS associated with essential hypertension in the most population, is the gene for angiotensin-converting enzyme- ACE). One DNA polymorphism within exon 2- with threonine instead of methionine at position 235 (M235T) was found to be significantly associated with hypertension. The objective of this study is the analysis of M235T polymorphism in angiotensinogen gene in Romanian patients with essential hypertension as well as controls. We examined 38 patients with essential hypertension and 21 normotensive patients. In order to identify the M235T angioteninogen variant, we used the following methods: DNA extraction, PCR amplification and enzymatic digestion of the PCR product using Tth 111I restriction endonuclease enzyme. In the study groups, the M235T variant (Met?Thr in aminoacid position 235) was found more frequently in hypertensive patients (81,57%), than in control subjects (66,66%). We identified 52,63% M235T heterozygotes in the hypertensive group compared with 47,61% in the control group, and 28,94% T235T homozygotes in the hypertensive group compared with 19,04% in the control group. The results of our study suggest an association of the M235T polymorphism in the gene encoding angiotensinogen with essential hypertension.
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PMID:Essential arterial hypertension and polymorphism of angiotensinogen M235T gene. 1216 9

To narrow the area known to contain the blood pressure quantitative trait locus (QTL) on rat chromosome 1, we constructed a fine linkage map covering the blood pressure OTL region on the chromosome using 22 genetic markers informative for stroke-prone spontaneously hypertensive rats of the Izumo colony (SHRSP/Izm) and Wistar-Kyoto rats of the Izumo colony (WKY/Izm). Linkage mapping was done by genotyping 626 backcrossed rats from matings between SHRSP/Izm and WKY/Izm. Nineteen genetic markers informative for the two strains were selected from public databases. Two markers were newly isolated by screening a rat genomic library. One marker was mapped using a restriction endonuclease polymorphism. The region between DlWox29 and D1Smu11 was covered with 22 informative markers placed every 0.6 cM on average. In addition, 6 physiological candidates for a hypertension gene were mapped in this region either by linkage or by radiation hybrid (RH) mapping. This information should be essential for the construction and analysis of congenic strains for this QTL region.
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PMID:Fine linkage mapping of the blood pressure quantitative trait locus region on rat chromosome 1. 1235 48

Gene encoding components of the renin angiotensin system (RAS) have been implicated with the increased risk of cardiovascular disease (CVD). Two variants of the angiotensinogen (AGT) gene, M235T and T174M, have been shown to be associated with increased risk of hypertension. In the present study, we examined the association of these two polymorphisms and their synergistic interaction with the angiotensin I-converting enzyme (ACE) deletion homozygote genotype (D/D) on subjects with coronary heart disease (CHD) and hypertension. We studied 131 healthy individuals, 141 angiographically verified CHD patients, and 159 hypertensive subjects. The identification of the ACE and AGT gene polymorphisms was carried out using a PCR-based restriction endonuclease digestion method. There was no significant difference in the distribution of the M235T and T174M variants between the two test groups and the control group. Association was also not seen when analysis was carried out in patients when subgrouped according to the extent of the severity of the disease. In addition, the risk was not restricted to subjects carrying the D allele of the ACE gene and T235T of AGT. M235T and T174M variants do not contribute to the increased risk of CHD or hypertension in the Indian population.
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PMID:Coronary heart disease, hypertension, and angiotensinogen gene variants in Indian population. 1293 41

Although the angiotensin converting enzyme (ACE) is a strong candidate gene for hypertension, the extensively studied insertion-deletion dimorphism in intron 16 was not found to be associated with it. Several new polymorphisms in the ACE gene were identified, among which a dimorphism in exon 17, ACE G2350A, has a significant effect on plasma ACE concentrations. To assess the value of genotyping the ACE G2350A dimorphism in a genetically homogeneous population, we carried out a retrospective, case-control study of dimorphism G2350A for a putative association with essential hypertension (EH) in a Gulf population (Emirati)--an ethnic group characterized by no alcohol intake and no cigarette smoking. We investigated a sample population of 254 Emirati, comprising 136 normotensive controls, and 118 patients with clinical diagnoses of EH. ACE G2350A alleles were visualized by assays based on polymerase chain reaction and restriction endonuclease analysis. The ACE G2350A dimorphism showed an association with EH (chi2=6.71, 2 df, P=0.05). Further analysis revealed that the ACE G/G 2350 genotype was positively associated (OR=1.06-3.07, P=0.02) with EH. This is the first association study of the ACE G2350A dimorphism with EH, and the positive result might indicate that ACE could be a QTL for EH as originally thought.
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PMID:Association of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with essential hypertension. 1450 31


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