Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. There is evidence to suggest that essential hypertension is a polygenic disorder and that it arises from yet-to-be-identified predisposing variants of certain genes that influence blood pressure. The cloning of various hormone, enzyme, adrenoceptor and hormone receptor genes whose products are involved in blood pressure control and the identification of polymorphisms of these has permitted us to test their genetic association with hypertension. 2. Cross-sectional analyses of a number of candidate gene markers were performed in hypertensive and normotensive subjects who were selected on the basis of both parents being either hypertensive or normotensive, respectively, and the difference in total alleles on all chromosomes for each polymorphism between the hypertensive and normotensive groups was tested by chi 2 analysis with one degree of freedom. 3. A marked association was observed between hypertension and insertion alleles of polymorphisms of the insulin receptor gene (INSR) (P < 0.0040) and the dipeptidyl carboxypeptidase-1 (angiotensin I-converting enzyme; kininase II) gene (DCP1) (P < 0.0018). No association with hypertension was evident, however, for polymorphisms of the growth hormone, low-density lipoprotein receptor, renal kallikrein, alpha 2- and beta 1-adrenoreceptor, atrial natriuretic factor and insulin genes. 4. All but one of the hypertensive subjects had at least one of the hypertension-associated alleles, and although subjects homozygous for both were three times more frequent in the hypertensive group, examination of the nine possible genotypes suggested that the INSR and DCP1 alleles are independent markers for hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Independent, marked associations of alleles of the insulin receptor and dipeptidyl carboxypeptidase-I genes with essential hypertension. 810 54

Increasing evidence suggests a relation between vascular disorders and late-onset Alzheimer's disease (AD). We performed an association analysis of low-density lipoprotein receptor-related protein (LRP), lipoprotein lipase (LPL), and angiotensin converting enzyme (ACE) genes, known to be involved in vascular disorders, and AD. Genotyping was carried out in 113 patients with clinically defined Alzheimer's disease (NINCDS-ADRDA criteria) and 203 non-demented controls in a prospective, population-based study of people aged 85 years or over (Vantaa 85+ Study). Corresponding analysis was performed on 121 neuropathologically verified AD patients (CERAD criteria) and 75 controls derived from the same study population. We did not find significant associations between the polymorphisms studied and AD. However, analysis of the LPL polymorphism showed a weak trend (uncorrected P-value 0.095) towards protection against neuropathologically defined AD. Our study is based on very elderly Finns. Therefore, further studies are warranted in other populations.
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PMID:Cardiovascular risk factors and Alzheimer's disease: a genetic association study in a population aged 85 or over. 1101 10

There is considerable enthusiasm for the prospect of using common polymorphisms (primarily single nucleotide polymorphisms; SNPs) in candidate genes to unravel the genetics of complex disease. This approach has generated a number of findings of loci which are significantly associated with sporadic Alzheimer's disease (AD). In the present study, a total of 15 genes of interest were chosen from among the previously published reports of significant association in AD. Genotyping was performed on polymorphisms within those genes (14 SNPs and one deletion) using Dynamic Allele Specific Hybridization (DASH) in 204 Swedish patients with sporadic late-onset AD and 186 Swedish control subjects. The genes chosen for analysis were; low-density lipoprotein receptor-related protein (LRP1), angiotensin converting enzyme (DCP1), alpha-2-macroglobulin (A2M), bleomycin hydrolase (BLMH), dihydrolipoyl S-succinyltransferase (DLST), tumour necrosis factor receptor superfamily member 6 (TNFRSF6), nitric oxide synthase (NOS3), presenilin 1 (PSEN1), presenilin 2 (PSEN2), butyrylcholinesterase (BCHE), Fe65 (APBB1), oestrogen receptor alpha (ESR1), cathepsin D (CTSD), methylenetetrahydrofolate reductase (MTHFR), and interleukin 1A (IL1A). We found no strong evidence of association for any of these loci with AD in this population. While the possibility exists that the genes analysed are involved in AD (ie they have weak effects and/or are population specific), results reinforce the need for extensive replication studies if we are to be successful in defining true risk factors in complex diseases.
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PMID:Lack of replication of association findings in complex disease: an analysis of 15 polymorphisms in prior candidate genes for sporadic Alzheimer's disease. 1143 25

While diabetes mellitus is most often associated with hypertension, dyslipidemia, and obesity, these factors do not fully account for the increased burden of cardiovascular disease in patients with the disease. This strengthens the need for comprehensive studies investigating the underlying mechanisms mediating diabetic cardiovascular disease and, more specifically, diabetes-associated atherosclerosis. In addition to the recognized metabolic abnormalities associated with diabetes mellitus, upregulation of putative pathological pathways such as advanced glycation end products, the renin-angiotensin system, oxidative stress, and increased expression of growth factors and cytokines have been shown to play a causal role in atherosclerotic plaque formation and may explain the increased risk of macrovascular complications. This review discusses the methods used to assess the development of atherosclerosis in the clinic as well as addressing novel biomarkers of atherosclerosis, such as low-density lipoprotein receptor-1. Experimental models of diabetes-associated atherosclerosis are discussed, such as the streptozocin-induced diabetic apolipoprotein E knockout mouse. Results of major clinical trials with inhibitors of putative atherosclerotic pathways are presented. Other topics covered include the role of HMG-CoA reductase inhibitors and fibric acid derivatives with respect to their lipid-altering ability, as well as their emerging pleiotropic anti-atherogenic actions; the effect of inhibiting the renin-angiotensin system by either ACE inhibition or angiotensin II receptor antagonism; the effect of glycemic control and, in particular, the promising role of thiazolidinediones with respect to their direct anti-atherogenic actions; and newly emerging mediators of diabetes-associated atherosclerosis, such as advanced glycation end products, vascular endothelial growth factor and platelet-derived growth factor. Overall, this review aims to highlight the observation that various pathways, both independently and in concert, appear to contribute toward the pathology of diabetes-associated atherosclerosis. Furthermore, it reflects the need for combination therapy to combat this disease.
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PMID:Diabetes mellitus-associated atherosclerosis: mechanisms involved and potential for pharmacological invention. 1648 46

Increased levels of low-density lipoproteins are well-established risk factors of endothelial dysfunction and the metabolic syndrome. In this study, we evaluated the effect of native low-density lipoprotein (nLDL) and oxidized LDL (oxLDL) on the expression of genes of the renin-angiotensin system (angiotensin-converting enzyme, ACE; angiotensin II type 1 receptor, AT(1)) and their receptors (low-density lipoprotein receptor: LDLR; lectin-like oxLDL receptor: LOX-1; toll-like receptor 4: TLR4) in primary cultures of human umbilical vein endothelial cells. ACE and AT(1) expressions were significantly increased after stimulation with nLDL and oxLDL. OxLDL receptor LOX-1 showed a maximum induction after 7 hours. Increased LOX-1 protein expression in response to oxLDL could be blocked by a LOX-1-specific antibody. TLR4 expression was increased by nLDL and oxLDL as well. We conclude that LDL and oxLDL can activate the renin-angiotensin system and their receptors LDLR, LOX-1, and TLR4 in human endothelial cells. These data suggest a novel link between hypercholesterolemia and hypertension in patients with the metabolic syndrome.
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PMID:Low-density lipoproteins induce the renin-angiotensin system and their receptors in human endothelial cells. 1799 34

The objective of this study was to assess the associations of presenilin 1 (PS1) 1/2, angiotensin I-converting enzyme (ACE) insertion/deletion (I/D), and low-density lipoprotein receptor-related protein (LRP) C/T polymorphisms with the risk of Alzheimer's disease (AD) in the Chinese population. PS1 1/2, ACE I/D, and LRP C/T, which are commonly investigated polymorphisms, were evaluated to obtain summary estimates regarding their associations with AD. In total, the data from 24 studies (2611 patients with AD and 2822 control subjects from 23 provinces and special districts in China) that were obtained from the Chinese Biomedicine Database, China National Knowledge Infrastructure, PubMed, and Medline were included. Different models (i.e., dominant, recessive, etc.) of these polymorphisms were analyzed using the Cochrane Review Manager. Statistically significant associations among patients with AD for the 1/1 genotype of the PS1 1/2 polymorphism [odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.03-3.04; P = 0.04] and the I/I genotype of the ACE I/D polymorphism (OR = 2.44, 95%CI = 1.78-3.35; P < 0.01) were identified. Statistically significant associations were also found for the PS1 1/2 polymorphism in both the dominant and recessive genetic models, whereas no association was found for the LRP C/T polymorphism. All studies exhibited heterogeneity (P < 0.05). This meta-analysis suggests that the 1/1 genotype of the PS1 1/2 polymorphism and the I/I genotype of the ACE I/D polymorphism are significantly associated with an increased risk of AD in the Chinese population.
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PMID:Association of PS1 1/2, ACE I/D, and LRP C/T polymorphisms with Alzheimer's disease in the Chinese population: a meta-analysis of case-control studies. 2573 41

Objective- AGT (Angiotensinogen) is the unique precursor of the renin-angiotensin system that is sequentially cleaved by renin and ACE (angiotensin-converting enzyme) to produce Ang II (angiotensin II). In this study, we determined how these renin-angiotensin components interact with megalin in kidney to promote atherosclerosis. Approach and Results- AGT, renin, ACE, and megalin were present in the renal proximal convoluted tubules of wild-type mice. Hepatocyte-specific AGT deficiency abolished AGT protein accumulation in proximal tubules and diminished Ang II concentrations in kidney, while renin was increased. Megalin was most abundant in kidney and exclusively present on the apical side of proximal tubules. Inhibition of megalin by antisense oligonucleotides (ASOs) led to ablation of AGT and renin proteins in proximal tubules, while leading to striking increases of urine AGT and renin concentrations, and 70% reduction of renal Ang II concentrations. However, plasma Ang II concentrations were unaffected. To determine whether AGT and megalin interaction contributes to atherosclerosis, we used both male and female low-density lipoprotein receptor-/- mice fed a saturated fat-enriched diet and administered vehicles (PBS or control ASO) or megalin ASO. Inhibition of megalin did not affect plasma cholesterol concentrations, but profoundly reduced atherosclerotic lesion size in both male and female mice. Conclusions- These results reveal a regulatory role of megalin in the intrarenal renin-angiotensin homeostasis and atherogenesis, positing renal Ang II to be an important contributor to atherosclerosis that is mediated through AGT and megalin interactions.
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PMID:Angiotensinogen and Megalin Interactions Contribute to Atherosclerosis-Brief Report. 3056 80