Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
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Homocysteine is a sulphur-containing amino acid formed during metabolism by one of two pathways by remethylation and transsulfuration. Altered homocysteine metabolism may be implicated as a factor in atherosclerosis, cerebrovascular disease or peripheral vascular disease. It is postulated that homocysteine may damage endothelial cells or acts as a direct causal factor in the thromboembolic process. Several studies have reported that there are a number of factors that may influence levels of homocysteine in humans. Serum homocysteine levels may be associated with low levels of folate, vitamin B6 and vitamin B12. These studies showed that serum homocysteine levels were higher in men and older adults, and some showed that there was a direct relationship between homocysteine and cigarette smoking, diabetes, obesity, and hypertension. Subjects who consume larger amounts of coffee were also noted to have higher serum homocysteine levels. Several cross-sectional, case-control, and cohort studies have linked homocysteinaemia with cardiovascular disease morbidity and mortality. In the Framingham Heart Study, the cohort study in Tromso, Norway, and the Atherosclerosis Risk in Communities (ARIC) Study, homocysteine levels were found to be higher in adults with asymptomatic or symptomatic coronary artery disease. In the British Regional Heart Study, homocysteine levels were found to be significantly higher in patients with stroke. Thus, there are suggestions that vitamin therapy and alteration of lifestyle habits such as cigarette smoking may lower homocysteine levels. There may be less coronary heart disease morbidity and mortality with lower homocysteine levels.
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PMID:Homocysteine and atherosclerotic disease: the epidemiologic evidence. 1056 72

Hyperhomocysteinemia is currently regarded as an independent and modifiable risk factor for ischemic vascular diseases and thrombosis. We measured fasting plasma total homocysteine levels by HPLC with fluorescence detection in 30 patients presenting with acute coronary syndromes and 30 age and sex-matched control subjects. Demographic data, classical risk factors (systolic blood pressure, diabetes mellitus, smoking, ethanol intake, family history of ischaemic heart disease) and life-style habits were recorded. Lipid fractions including total cholesterol, triglycerides, HDL-cholesterol, total cholesterol/HDL-cholesterol ratio, serum creatinine, LDL-cholesterol and vitamins involved in the metabolism of homocysteine, folic acid and vitamin B12 were also assessed. Total fasting homocysteine concentrations were significantly higher in the patient group (12.2 +/- 1.01 micromol/l) than in the control subjects (7.05 +/- 0.36 micromol/l; p < 0.0001). Homocysteine correlated positively with age (r = 0.617; p < 0.01) and serum creatinine (r = 0.457; p < 0.01) in the patient group. Hyperhomocysteinemia was not associated with vitamin B12 or folate deficiency states. Vitamin B12 concentration was 273 +/- 16.4 ng/l in the control group and 284.3 +/- 32.2 ng/l in the patient group (p = NS). Serum folate concentration also was not significantly different between controls and patients; 7.57 +/- 0.58 microg/l and 8.05 +/- 0.72 microg/l, respectively. Since no significant difference was observed in the lipid parameters between patients and controls, the hyperhomocysteinemia in the patient group supports the view that homocysteine is an independent risk factor for cardiovascular diseases. Our results strongly suggest that elevated homocysteine levels are among the interacting factors in the complex, multifactorial pathophysiology of ischemic heart disease.
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PMID:Plasma homocysteine levels in acute coronary syndromes. 1073 56

We assessed the contribution of the serum homocysteine (Hcy) level, an independent risk factor for vascular disease, and methylene tetrahydrofolate reductase (MTHFR) gene polymorphism to the variability of intimal-medial thickness (IMT) of the common carotid artery in middle-aged non-insulin-dependent diabetes mellitus (NIDDM) subjects. One hundred thirty NIDDM patients (60 males and 70 females) with a mean age of 53 +/- 10 years and a mean diabetes duration of 11.3 +/- 7.9 years were enrolled for the study. Exclusion criteria included liver, heart, kidney, or other major-organ disease. Fasting total serum Hcy, folate, and vitamin B12 and clinical chemistry analyte levels were measured. MTHFR polymorphism was determined by polymerase chain reaction (PCR). IMT and plaques or stenosis in the common carotid were measured by ultrasonography. Serum Hcy was inversely correlated with vitamin levels and was slightly higher in subjects with the Val/Val genotype versus Ala/Val and Ala/Ala (P = .02); no differences in genotype were found in subjects with folate or vitamin B12 at or above the median level. In univariate analysis, common carotid IMT was significantly associated with age (P = .00001), the body mass index ([BMI] P = .0003), uric acid (P = .004), systolic blood pressure (P = .03), glycemia (P = .03), and total cholesterol (P = .04). No significant association was found between serum Hcy or MTHFR polymorphism and IMT. In multiple regression analysis, age (P = .0001), uric acid (P = .03), glycemia, and the BMI (P = .05) were independently associated with IMT and explained about 42% of IMT variability. In 130 NIDDM patients without nephropathy, basal levels of serum Hcy, as well as MTHFR polymorphism, did not predict significant changes in common carotid IMT.
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PMID:Lack of association between carotid intima-media thickness and methylenetetrahydrofolate reductase gene polymorphism or serum homocysteine in non-insulin-dependent diabetes mellitus. 1087 95

Observational studies support the role of modifying lifestyle-related risk factors such as diet, physical activity and alcohol use in stroke prevention. For example, increased Na intake is associated with hypertension, and reduction in salt consumption may significantly lower blood pressure and may reduce stroke mortality. Moderately elevated homocysteine levels may be associated with stroke and are associated with deficiency of dietary intake of folate, vitamin B6 and vitamin B12. Consumption of a diet rich in fruits, vegetables, folate, K, Ca, Mg, dietary fibre, fish and milk may protect against stroke. Regular physical activity may also protect against stroke through its role in controlling various risk factors such as hypertension, diabetes mellitus and obesity. The role of fat intake as a risk factor for stroke remains uncertain, whereas the association between stroke and cholesterol has more convincingly been demonstrated by the recent intervention trials using statins. There is also evidence that a low serum albumin may be causally linked to stroke risk and outcome and that a significant number of stroke patients are undernourished on admission and their nutritional status deteriorates further whilst in hospital. Undernutrition is associated with increasing morbidity and mortality and nutritional supplements may have some beneficial effect on some outcome measures.
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PMID:Nutritional factors in stroke. 1096 Nov 55

The genetic information stored in the DNA is transmitted to an RNA molecule through transcription and protein molecules are obtained from the RNA using translation techniques. Each of the processes forming part of this chain is the object of complex regulation (gene expression regulation). Some nutrients may affect gene expression by taking part in these regulatory mechanisms, such as sterols, glucose, vitamins A, D and B12, various fatty acids or some components of dietary fibre. These phenomena may have come about through the adaptation of the primitive beings to the various changes in the nourishment available. The successive changes over centuries have led to the determination of individuals' phenotypes not only by their genotype but also by environmental factors such as diet. Our genes have adapted to the changing sources of nourishment surrounding our ancestors; modern diets are, however, very different from those of the past. The inability of our genetic store to adapt to modern diets may be the reason for the appearance of certain chronic diseases in developed countries. One well-analyzed case is that of the thrifty genotype which provided evolutionary advantages in the past, but may now be contributing to obesity and diabetes. Further examples of genotype interaction with various environmental factors to produce different phenotypes are provided by the apolipoproteins: some mutations in the genes of these proteins, in combination with different diet types, are associated with altered lipid levels and the risk of various cardiovascular diseases. These diet-genotype interactions mean that it is fundamentally important to take into account the genetic variability of individuals before recommending dietary measures to prevent the so-called "first-world" diseases.
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PMID:[Nutrition and gene expression]. 1121 97

In order to evaluate the clinical characteristics of metabolic syndrome, a screening procedure was performed and in a cohort of middle-aged (40-60 years) hyperinsulinaemic (fasting plasma insulin > 15 microU/ml) and/or postprandial [120 min after 75 g glucose load] insulin > 45 microU/ml) subjects (n = 91; men/women: 38/53; age mean +/- SD 47.6 +/- 4.3 years; body mass index: 34.6 +/- 4.9 kg/m2; waist-hip ratio: 0.92 +/- 0.07; actual blood pressure 146 +/- 16/87 +/- 9 mmHg; fasting insulin: 24.2 +/- 11.3 microU/ml; postprandial insulin 125.5 +/- 103.8 microU/ml; serum LDL-cholesterol: 3.73 +/- 1.09 mmol/l; HDL-cholesterol: 1.12 +/- 0.30 mmol/l; triglycerides: 2.97 +/- 2.38 mmol/l; uric acid 279 +/- 79 mumol/l) plasma fasting homocysteine, vitamin B12 and folic acid levels were simultaneously determined. The values were separately evaluated according to the stages of glucose tolerance (normal glucose tolerance [n = 47]; impaired glucose tolerance [n = 24] and diabetes mellitus [n = 20]). Laboratory normal values were determined in 47 healthy subjects (control group, age: 45.0 +/- 7.8 years, men/women: 19/28). There was no significant difference between hyperinsulinaemic and control subjects regarding plasma homocysteine (9.28 +/- 3.81 mumol/l vs. 9.63 +/- 2.70 mumol/l), folic acid (8.5 +/- 5.9 ng/ml vs. 7.5 +/- 2.1 ng/ml) and vitamin B12 levels (423 +/- 141 pg/ml vs. 356 +/- 121 pg/ml). Plasma homocysteine levels were significantly (p < 0.001) higher in hyperinsulinaemic men than women (11.34 +/- 4.72 mumol/l [n = 38] vs. 7.86 +/- 2.13 mumol/l [n = 53]). There was no significant difference between subgroups classified according to the stages of glucose tolerance in hyperinsulinaemic groups. Plasma homocysteine values exceeding the upper limit of normal range (> 12.45 mumol/l) were detected at a similar prevalence rate in control (4/47 = 8.5%) and in hyperinsulinaemic subjects (10/91 = 10.9%). A weak but statistically significant correlation was found between plasma homocysteine values and age of subjects (r = 0.222; p < 0.05) whereas a stronger correlation was documented between plasma homocysteine and serum creatinine values (r = 0.658; p < 0.001) in hyperinsulinaemic groups (n = 91). Plasma homocysteine values independently from the stages of glucose tolerance are not elevated in hyperinsulinaemic subjects. Hyperhomocysteinaemia is not a characteristic feature of hyperinsulinism suggesting that plasma homocysteine levels are of no considerable importance in the complex pathomechanism of atherosclerosis at early stages of metabolic syndrome.
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PMID:[Plasma homocysteine levels in hyperinsulinemic patients]. 1124 22

Stroke is a major cause of morbidity and mortality. Risk factors for stroke have been determined through prospective epidemiologic study. Control of risk factors has been demonstrated to reduce stroke incidence, either through controlled trials or inferred from observational studies. In the past few years, new approaches to the treatment of established risk factors have been discovered. These include aggressive control of hypertension in diabetes patients, prevention of type 2 diabetes through lifestyle modification, carotid endarterectomy for moderate symptomatic carotid stenosis, encouragement of a high level of physical activity, and control of abdominal obesity and elevated body mass index. In addition, new strategies for stroke prevention have been identified, including encouragement of a diet high in fruits, vegetables, whole grains, and omega-3 fatty acids, the use of vitamins B12, B6, and folic acid in hyperhomocysteinemia, and moderate alcohol consumption. Clinical trial data support the use of hydroxy-methyl-coenzyme A inhibitors in patients with coronary artery disease, and ramipril in high-risk patients with coronary artery disease and diabetes, for the primary prevention of stroke. New risk factors for stroke are being investigated, including the role of chronic inflammation and infection, and these may provide future strategies for stroke prevention.
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PMID:Prevention of strokes. 1138 98

Cardiovascular disease is the leading cause of mortality in Mexico, as well as in other Western countries. Conventional risk factors for atherosclerosis, such as cigarette smoking, systemic hypertension, diabetes mellitus, and hypercholesterolemia, do not explain this association completely. Recently, it has been recognized that hyperhomocysteinemia contributes to the atherosclerotic process, promoting endothelial damage and oxidative stress in the vascular wall. Homocysteine, an amino acid generated under physiologic conditions after ingestion of protein-rich foods, is used in a variety of metabolic pathways. Elevated plasma levels of this amino acid (higher than 15 mmol/L or lower in the presence of other cardiovascular risk factors) promote the development of atherosclerosis. Folic acid and vitamin B6 and B12 supplements decrease plasma levels of homocysteine effectively and may play an important role in the prevention and treatment of atherosclerotic vascular disease.
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PMID:[Hyperhomocysteinemia. A new coronary risk factor]. 1151 57

Elevated serum total homocysteine, an established risk factor for peripheral arterial disease, is influenced by the vitamin B12 and folate status. Since these vitamins are inversely correlated with erythrocyte mean corpuscular volume, an investigation of whether mean corpuscular volume is higher in patients with symptomatic peripheral arterial disease than in healthy subjects was performed. Furthermore, a determination of predictors of increased mean corpuscular volume levels in this population free of symptomatic coronary artery disease, cerebrovascular disease, and diabetes mellitus was carried out. From 469 consecutive patients with symptomatic peripheral arterial disease, 100 fulfilled study inclusion criteria. Peripheral arterial disease was confirmed by angiography. One hundred age-matched subjects without peripheral arterial disease as verified by ankle-brachial index measurements >0.9 served as control subjects. Patients with PAD displayed a significantly higher mean corpuscular volume level (94.5 fl) than control subjects (90.9 fl, p<0.001). Logistic regression analysis showed that current smoking status (p<0.001) and mean corpuscular volume (p=0.009), but not total homocysteine or lipid parameters discriminated case control status. In addition, logistic regression analysis revealed a relationship of mean corpuscular volume with smoking (p=0.001), gamma-glutamyltransferase (p<0.001), and total homocysteine (p=0.012). This model predicted mean corpuscular volume values with an accuracy of 83%. Elevated mean corpuscular volume is a predictor of symptomatic peripheral arterial disease in the sample studied. A deficiency of folate and/or vitamin B12 may be responsible for this observation, as indicated by the correlation of mean corpuscular volume with total homocysteine. Due to the additional association of mean corpuscular volume with smoking and gamma-glutamyltransferase, an unhealthy lifestyle with low vitamin intake may cause elevated mean corpuscular volume values in patients with PAD.
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PMID:Association between erythrocyte mean corpuscular volume and peripheral arterial disease in male subjects: a case control study. 1157 Jun 59

Hyperhomocysteinemia is the result of a disturbed methionine metabolism. It results from enzyme and/or vitamin deficiency. Epidemiological studies have proven, that hyperhomocysteinemia is a risk factor for atherosclerotic cardiovascular diseases, stroke, peripheral arterial occlusive disease and venous thrombosis. Conflicting results come from prospective studies. Trials which are now in progress may clarify the "causality" of high homocysteine concentrations and will assess the value of homocysteine-lowering therapy. The induction of the atherogenic process by hyperhomocysteinemia seems to be associated with an alteration of endothelial and smooth muscle cell function leading to an accelerated formation of reactive oxygen species. An increased endothelial expression of adhesion molecules will then lead to an enhanced deposition of oxidized LDL in the vessel wall with the formation of foam cells. Additionally, hyperhomocysteinemia interferes with the coagulation system and thus also has prothrombotic effects. There is a high prevalence of hyperhomocysteinemia as a sign of a vitamin deficiency in elderly subjects which strongly increases with age. Elderly people have a high frequency of vitamin B12 deficiency which can be diagnosed more reliably by the measurement of serum methylmalonic acid (MMA) level than by serum vitamin B12. Subjects following a strict vegetarian diet also have a high prevalence of hyperhomocysteinemia caused by functional vitamin B12 deficiency (increased MMA level). Last but not least, hyperhomocysteinemia is a factor in the pathogenesis of neural tube defects and pre-eclampsia. An early diagnosis of vitamin B12 deficiency is important for the prevention of neurological damages. Homocysteine should be measured in patients with a history of atherothrombotic vessel diseases, in patients with diabetes or hyperlipidemia, in renal patients, in obese subjects, in elderly people, in postmenopausal women, and in early pregnancy. A specific diagnosis of an underlying vitamin deficiency is important for adequate treatment. Individuals with homocysteine level >12 micromol/l should increase and/or supplement their dietary intake of vitamins.
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PMID:The importance of hyperhomocysteinemia as a risk factor for diseases: an overview. 1159 31


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