Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiological, population and familial studies have revealed the multifactorial aspect of diabetes mellitus. Several mutations implicated in the pathogenesis of diabetes have been described over the last decade. These mutations are localised within genes associated with glucose metabolism, providing a molecular basis for the heterogeneity in the clinical presentation of diabetes mellitus. However, chronic hyperglycaemia associated with other vascular risk factors can only partly explain the incidence of micro and macrovascular complications. Familial studies have revealed the presence of a familial susceptibility for some vascular complications as nephropathy and coronary heart disease. In addition, these two vascular complications of diabetes mellitus are frequently associated in the same individual. This familial susceptibility could not be exclusively explained by environmental factors. Consequently the quest for susceptibility genes of vascular complications appears as a logical approach. The study of genes associated with an increased cardiovascular risk like the renin angiotensin system, the hemostasis cascade or the lipoproteins, may constitute the first step in this new research avenue. Moreover, glycation and oxidation pathways seem to play a role in the development of vascular complications. For example, the paraoxonase genes are good candidates for an increased vascular risk. This enzyme is entirely bound to HDL-cholesterol and could explain its anti-oxidant capacity. The natural substrate of this enzyme is unknown but there is some evidence suggesting that it may participate in the oxidated phospholipids degradation. Functional studies of paraoxonase with other exogenous substrates have revealed different phenotypes associated with different catalytic activities. In addition, varying enzymatic activities seem to be associated with different polymorphisms of the paraoxonase gene recently described (at position 192 and 55 of the paraoxonase gene), and these two polymorphisms have been recently studied in relation with coronary heart disease in non insulin dependent diabetic patients. The two polymorphisms were associated with coronary heart disease. But these initial results still await confirmation in different populations. Such studies will likely open the way to novel approach of vascular complications in diabetes mellitus.
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PMID:Diabetes mellitus and the late complications: influence of the genetic factors. 910 85

Previously, we demonstrated increased Angiotensin II type I receptor expression in leukocytes from patients with untreated, but not in treated, essential hypertension (essential hypertension). We hypothesized that the Angiotensin II AT1 receptor is also increased in leukocytes from patients with chronic kidney disease, however and can still be corrected with combined anti-hypertensive treatment with renin-angiotensin system (RAS) blockers and statins. Blood pressure, cholesterol, renal function oxidative stress parameters, inflammation, and leukocyte Angiotensin II AT1 receptor mRNA expression were measured both on and (6 weeks) off treatment. Data were compared to data of 10 healthy control subjects. Untreated chronic kidney disease patients (n=20) had higher blood pressure, cholesterol and leukocyte Angiotensin II AT1 receptor mRNA expression, but no different ox-LDL, thiobarbituric acid reactive substances, paraoxonase activity or hs-CRP. OxLDL and Lipoprotein(a) were increased in untreated chronic kidney disease. Angiotensin II AT1 receptor expression inversely correlated with renal function (R(2)=0.15, P<0.03) and Lipoprotein(a) but not with the other parameters. Treatment with RAS blockers and statins normalized blood pressure and cholesterol, however it did not correct enhanced leukocyte Angiotensin II AT1 receptor expression. Leukocyte Angiotensin II AT1 receptor expression is inappropriately high in chronic kidney disease, correlates inversely with renal function and does not depend on antihypertensive and lipid-lowering treatment. The uremic environment seems to dominate over previously reported actions of high blood pressure and cholesterol to enhance leukocyte Angiotensin II AT1 receptor expression.
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PMID:Enhanced Angiotensin II type 1 receptor expression in leukocytes of patients with chronic kidney disease. 2164 98