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)

The homozygous deletion allele of the angiotensin-converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the epsilon4 allele of the apolipoprotein E gene (apoE/epsilon4) are reported to be associated with ischemic heart disease. Cerebral infarction (CI) is another atherosclerotic disease, and the effects of these polymorphisms on CI have been confusing. The frequency of the DD genotype of the ACE gene, but not the TT genotype of the AGN gene and the epsilon4 allele of ApoE, was significantly higher in subjects with than those without CI in Japan. In this study, we investigated whether ACE/DD, AGN/TT, and apoE/epsilon4 genotypes are associated with CI and whether genetic risk is enhanced by the effect of one upon another. We ascertained these genotypes in patients with CI (n = 365), diagnosed by brain computed tomography. Control subjects for the infarction group were randomly selected from 319 subjects matched for age, gender, and history of hypertension with patients. The ACE/DD genotype was not associated with CI. Frequency of the AGN/TT genotype was higher in patients with CI than in controls (chi2 = 12.287, p < 0.05). The frequency of t allele was 0.88 in patients and 0.82 in controls (chi2 = 11.041, p < 0.05; odds ratio, 1.7). Furthermore, the AGN/TT genotype increased the relative risk for CI in subjects with the ACE/DD genotype (chi2 = 7.8, p < 0.05; odds ratio, 1.9). There was no significant association between apoE/epsilon4 and CI. These results suggest that AGN/TT predicts CI and ACE/DD enhances the risk for CI associated with AGN/TT in a Korean population.
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PMID:Polymorphism of angiotensin-converting enzyme, angiotensinogen, and apolipoprotein E genes in Korean patients with cerebral infarction. 1450 Sep 90

The literature on the association between apolipoprotein E (ApoE) and mortality across ethnic and age groups has been inconsistent. No studies have looked at this association in developing countries. We used data from the Indianapolis-Ibadan Dementia study to examine this association between APOE and mortality in 354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria. Participants were followed up to 9.5 years for Indianapolis and 8.7 years for Ibadan. Subjects from both sites were divided into 2 groups based upon age at baseline. A Cox proportional hazards regression model adjusting for age at baseline, education, hypertension, smoking history and gender in addition to time-dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was fit for each cohort and age group. Having ApoE epsilon4 alleles significantly increased mortality risk in Indianapolis subjects under age 75 (hazard ratio: 2.00; 95% CI: 1.19-3.35; p = 0.0089). No association was found in Indianapolis subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45-1.10; p = 0.1238), Ibadan subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274).
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PMID:Apolipoprotein E and mortality in African-Americans and Yoruba. 1464 29

Lacunar brain infarcts and cerebral white matter lesions are frequently observed on magnetic resonance imaging scans in elderly subjects. These lesions are also frequent in patient with cerebral amyloid angiopathy. We examined whether plasma amyloid beta peptide (Abeta) levels are associated with lacunar infarcts and white matter lesions in the general population, and whether the apolipoprotein E (APOE) genotype modifies these associations. We studied 1,077 participants within the population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia. Cross-sectional associations were analyzed by regression models with adjustments for age, sex, creatinine levels, and hypertension. In APOE epsilon4 carriers, plasma Abeta levels were positively associated with lacunar infarcts and white matter lesions, whereas in noncarriers no associations were observed. Per standard deviation increase in Abeta(1-40) and Abeta(1-42) levels the odds ratios for lacunar infarcts were 1.72 (95% confidence interval [CI] = 1.22-2.43) and 1.93 (95% CI = 1.31-2.85), the periventricular white matter lesion grade increased by 0.32 (95% CI = 0.08-0.57) and 0.29 (95% CI = 0.00-0.57), and the subcortical white matter lesion volume increased by 0.48 ml (95% CI = 0.04-0.91) and 0.24 ml (95% CI = -0.27-0.75). Higher Abeta levels are associated with more lacunar infarcts and white matter lesions in elderly subjects who carry an APOE epsilon4 allele.
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PMID:Plasma amyloid beta, apolipoprotein E, lacunar infarcts, and white matter lesions. 1504 97

Given that a substantial proportion of individuals with coronary artery disease (CAD) also have type 2 diabetes, it is important to identify genes that confer susceptibility to CAD independently in subjects with type 2 diabetes and in those without this condition. A large-scale association study was performed to identify genes that confer susceptibility to CAD in either the absence or presence of type 2 diabetes. The study population comprised 5207 unrelated Japanese individuals, including 3085 subjects with CAD and 2122 controls. Among all subjects, 1704 individuals had type 2 diabetes and 3503 individuals did not have this condition. The genotypes for 33 polymorphisms of 27 candidate genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, hypertension, hypercholesterolemia, and hyperuricemia revealed that the following polymorphisms were significantly (P < 0.005) associated with CAD: the 1019C -->T of the connexin 37 gene for men with type 2 diabetes; the 2445G -->A in the fatty acid-binding protein 2 gene for women with this condition; the -863C-->A in the tumor necrosis factor-alpha gene, the -219G-->T in the apolipoprotein E gene, the 1019C-->T in the connexin 37 gene for men without type 2 diabetes; and the -482C-->T in the apolipoprotein C-III gene for women without this condition. Genotyping of these polymorphisms may prove informative for assessment of the genetic risk for CAD in the absence or presence of type 2 diabetes.
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PMID:Genetic risk for coronary artery disease in individuals with or without type 2 diabetes. 1505 15

The aims of neurology in Japan in the 21st Century should include establishment of therapeutic measures for neurological diseases, training clinical neurologists to cover both static and dynamic aspects of neurology, and application of gene therapy and neurogenesis to clinical neurology. It is also important to note that once any neurological disease develops, remaining sequelae are usually not curable, so the problem of how to prevent the onset of neurological diseases, that is preventive neurology, will become increasingly important. The key target for prevention in neurology is cerebro-vascular disease, since it is very common. Many risk factors are known for ischemic CVD. However, even for the management of hypertension, the so-called number needed to treat (NNT) is 29-118/5 years for primary prevention and 14-23/5 years for secondary prevention. It is also important to consider genetic factors that influence CVD, including abnormal plasminogen, Lp (a), ACT Isehara 1 gene, apolipoprotein E and so on, since these congenital factors reinforce known acquired risk factors, such as hypertension. In addition, the presence of asymptomatic cerebral infarction, as well as PVH and DSWMH, in MRI T2-weighted images is an important predictor of future symptomatic CVD. Finally, storage of one's own bone marrow cells might be useful, since in the event of onset of CVD, dementia or other neurological diseases, autotransplantation with cytokine might become available for neurogenesis. The results of our recent experiments indicate that this idea may be feasible.
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PMID:[Neurology in the 21st century--the era of preventive neurology utilizing new diagnostic and therapeutic techniques]. 1515 50

Hippocampal atrophy (HA) is usually attributed to the neurofibrillary tangles and neuritic plaques of Alzheimer disease. However, the hippocampus is vulnerable to global ischemia, which may lead to atrophy. We investigated the association of midlife blood pressure (BP) and late-life HA in a sample of Japanese-American men born between 1900 and 1919. BP was measured on 3 occasions between 1965 and 1971. In 1994 to 1996 a subsample underwent magnetic resonance imaging (MRI) of the brain. Hippocampal volume was estimated by manually drawing regions of interest on relevant scan slices; HA was defined as the lowest quartile of hippocampal volume. Also assessed on the MRI were cortical and subcortical infarcts, lacunes, and white matter hyperintensities. The risk (OR, 95% CI) was estimated for HA associated with systolic (<140 versus > or =140 mm Hg) and diastolic (<90 versus > or =90 mm Hg) BP and with antihypertensive treatment. Analyses were adjusted for sociodemographic factors, other cardiovascular risk factors, apolipoprotein E allele, and correlated brain pathology. Those never treated with antihypertensive medication had a significantly increased risk for HA (OR 1.7; CI=1.12; 2.65). The nontreated subjects with high systolic BP had an increased risk (OR=1.98; CI=0.89; 4.39) for HA. Results were similar for untreated men with high diastolic BP (OR=3.51; CI=1.26; 9.74). In conclusion, treatment with antihypertensive treatment modifies the association of BP and HA, such that high levels of BP adversely affect the hippocampus in persons never treated with antihypertensives.
Hypertension 2004 Jul
PMID:Midlife blood pressure and the risk of hippocampal atrophy: the Honolulu Asia Aging Study. 1517 24

3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, or statins, are widely prescribed to lower cholesterol. Recent reports suggest that statins may promote angiogenesis in ischemic tissues. It remains to be elucidated whether statins potentially enhance unfavorable angiogenesis associated with tumor and atherosclerosis. Here, we induced hind limb ischemia in wild-type mice by resecting the right femoral artery and subsequently inoculated cancer cells in the same animal. Cerivastatin enhanced blood flow recovery in the ischemic hind limb as determined by laser Doppler imaging, whereas tumor growth was significantly retarded. Cerivastatin did not affect capillary density in tumors. Cerivastatin, pitavastatin, and fluvastatin inhibited atherosclerotic lesion progression in apolipoprotein E-deficient mice, whereas they augmented blood flow recovery and capillary formation in ischemic hind limb. Low-dose statins were more effective than high-dose statins in both augmentation of collateral flow recovery and inhibition of atherosclerosis. These results suggest that statins may not promote the development of cancer and atherosclerosis at the doses that augment collateral flow growth in ischemic tissues.
Hypertension 2004 Jun
PMID:Statins augment collateral growth in response to ischemia but they do not promote cancer and atherosclerosis. 1516 78

The lipoprotein(a) [Lp(a)] and apolipoprotein E (apoE) polymorphisms have been shown to be important genetic determinants of cardiovascular risk. Their effect on coronary heart disease (CHD) is less clear, particularly in Asian Indians who are at high risk for this disease. The aim of this study was to examine the association of the Lp(a) promoter pentanucleotide repeat polymorphism and the apoE codon 112 and 158 genotypes in 195 young South African Indian patients (< or = 45 years) with myocardial infarction (MI). Results were compared with 300 healthy age-matched control subjects drawn from the same community and 107 unaffected siblings (18-45 years). In addition, fasting lipograms were performed on all patients and a detailed history of conventional risk factors and family background was obtained. Of the six different Lp(a) alleles detected, the 8-repeat sequence was most frequently seen. However, no difference in frequencies existed between patient and control groups. The most frequently occurring apoE genotype in the three study groups was E3/E3 (patients 71%; siblings 70%; controls 70%). A significant difference in the E3/E4 genotype was seen between patients and controls (23% vs 14%; p = 0.018) and between siblings and controls (24% vs 14%; p = 0.027). These patients were also more likely to have significantly higher low-density lipoprotein (LDL) and lower high-density lipoprotein (HDL) levels (p = 0.005 and 0.045, respectively). No association was observed between any of the Lp(a) or apoE genotypes and conventional risk factors such as smoking, diabetes, hypertension, obesity or a family history of CHD. In conclusion, the apoE3/E4 genotype is strongly associated with the incidence of myocardial infarction in young South African Indians. This genotype also adversely affects LDL and HDL cholesterol levels, both of which contribute to premature atherosclerosis. In contrast, the Lp(a) pentanucleotide repeat polymorphism does not appear to have any aetiological role in MI in this population.
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PMID:Lp(a) and apoE polymorphisms in young South African Indians with myocardial infarction. 1525 20

Recently, there has been an explosion in the number of in vivo studies using genetically engineered mouse models. Atherosclerosis research using mice began with the invention of traditional atherosclerotic mice including low-density lipoprotein receptor knockout (LDLR(-/-)) and apolipoprotein E knockout (apoE(-/-)) mice, which provided tremendous progress in atherosclerosis research. Since then, a number of modified atherosclerotic mouse models have been reported to generate lesions that more closely characterize human atherosclerotic lesions. Those modifications include inflammation, hypertension, proteinases and extracellular matrix, glucose metabolism, and immune systems. This article focuses on various kinds of mouse models with atherosclerosis and their contributions to the current advances of research.
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PMID:Cellular and molecular mechanisms of atherosclerosis with mouse models. 1526 90

Obesity is associated with increased incidence of cardiovascular mortality. However, the mechanisms that link increased fat mass with hypercholesterolemia, hypertension, endothelial dysfunction and coronary heart disease have not been fully elucidated. Unravelling the diverse neuroendocrine systems, which regulate energy balance and body fat has been a long-standing challenge in biology, with obesity as an increasingly important public health focus. Until recently, the adipocyte has been considered only a passive tissue for the storage of excess energy in the form of fat. However, there is now compelling evidence that adipocytes act as endocrine, secretory cells. It has been shown that several hormones, growth factors and cytokines are actually expressed in white adipose tissue. In a dynamic view of the adipocyte a wide range of signals emanates from white adipose tissue such as tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and their respective soluble receptors. White adipose tissue also secretes important regulators of lipoprotein metabolism like lipoprotein lipase (LPL), apolipoprotein E (apoE) and cholesteryl ester transfer protein (CETP). The increasing number of products secreted by adipocytes also includes leptin, estrogen, angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), tissue factor and transforming growth factor-beta (TGF-beta). Nitric oxide synthase (NOS) has been also reported to be expressed in white adipose tissue. Acylation stimulating protein (ASP), adipophilin, adipoQ, adipsin, monobutyrin, agouti protein and factors related to pro-inflammatory and immune processes have also been shown to be released by white adipocytes. Since blood vessels express receptors for most of the adipocyte-derived factors, adipose tissue seems to play a key role in cardiovascular physiology through the existence of a network of local and systemic signals. The current knowledge in this field will be reviewed in the broader perspective of cardiovascular physiology and pathophysiology.
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PMID:The adipose tissue as a source of vasoactive factors. 1532 Jul 86


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