Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The apolipoprotein (a) [apo(a)] gene encodes a protein component of lipoprotein (a) [Lp(a)] whose plasma levels vary among individuals. To study the implications of Lp(a), we examined plasma Lp(a) levels and molecular weights of apo(a) in patients with cerebrovascular disease (CVD) or diabetes mellitus (DN). Mean Lp(a) concentrations were higher in the CVD cases with atherothrombotic brain infarction than in those with brain hemorrhage and lacunar infarction. Lp(a) levels were lower in the DM cases on diet therapy alone than in those treated with insulin or oral hypoglycemic agents. These results suggest that Lp(a) is thrombogenic and atherogenic, and that insulin may modulate Lp(a) levels. We subclassified the apo(a) gene into four types (A-D) by polymorphisms in the 5'-flanking region. We also measured plasma Lp(a) concentrations and examined expression of the gene by an in vitro assay. Homozygotes of type C had higher Lp(a) levels than those of type D, and the relative expression of type C was higher than that of type D in vitro. Lp(a) levels, however, varied even within the same 5'-allele having similar apo(a) isoforms. Thus, Lp(a) concentrations are genetically determined and may be modified by some hormones and cytokines. When we examined transcript levels for apo(a) by RT-PCR in various normal tissues, apo(a) was strongly expressed in liver while not in thyroid or leukocytes. Small amounts of apo(a) transcript were observed in all other organs and tissues. Apo(a) in these tissues may also play a role in inframmation, tissue remodeling, cell migration, and other physiological functions.
 ...
PMID:Multi-modal expression of apolipoprotein (a) gene in vivo. 973 Jan 41

Patients with end-stage renal disease treated by hemodialysis have a tremendous risk for cardiovascular complications that cannot be explained by traditional atherosclerosis risk factors. Lipoprotein(a) (Lp(a)), a risk factor for these complications in the general population, is significantly elevated in these patients. In this study, it was determined whether Lp(a) and/or the genetically determined apo(a) phenotype are risk predictors for the development of coronary artery disease in these patients. A cohort of 440 unselected hemodialysis patients were followed for a period of 5 yr independent of the cause of renal disease, duration of preceding treatment, and the preexistence of coronary artery disease at study entry. Coronary events defined as definite myocardial infarction, percutaneous transluminal coronary angioplasty, aortocoronary bypass, or a stenosis >50% in the coronary angiography were the main outcome measure. Sixty-six (15%) of the 440 patients suffered a coronary event during follow-up. In univariate analysis, patients with events were significantly older and showed a trend to lower HDL cholesterol concentrations, and higher apolipoprotein B and Lp(a) concentrations without reaching significance. Apo(a) phenotypes of low molecular weight, however, were significantly more frequent in patients with compared to those without events (43.9% versus 21.9%, P<0.001). The other lipids, lipoproteins, and apolipoproteins were similar in both groups. Multiple Cox proportional hazards regression analysis found age and the apo(a) phenotype to be the best predictors for coronary events during the observation period, independent of whether patients with a preexisting coronary artery disease or an age >65 yr at the study entry or both were excluded from the analysis. Diabetes mellitus was a risk factor only in presence of a low molecular weight apo(a) phenotype. The genetically determined apo(a) phenotype is a strong and independent predictor for coronary events in hemodialysis patients. Apo(a) phenotyping might be helpful to identify hemodialysis patients at high risk for coronary artery disease.
 ...
PMID:The low molecular weight apo(a) phenotype is an independent predictor for coronary artery disease in hemodialysis patients: a prospective follow-up. 1023 89

Apolipoprotein(a) [apo(a)] is the specific apolipoprotein of lipoprotein(a) [Lp(a)], a recognized cardiovascular risk factor. Apo(a) is characterized by a high genetic polymorphism with at least 34 isoforms in plasma. Recent studies have shown that in atherothrombosis apo(a) polymorphism could play a role independent of Lp(a) levels. In particular, apo(a) phenotypes seem to have their highest predictive value for coronary heart disease, when apo(a) isoforms are detected by high resolution phenotyping methods and when an adequate operative cut-off of apo(a) polymorphism is used. A strong association between apo(a) phenotypes and coronary heart disease has been also found in hypertensive, diabetic, and uremic patients. Moreover, apo(a) phenotypes seem to correlate well with the severity of coronary atherosclerosis and the age of clinical onset of coronary heart disease. These studies suggest that apo(a) polymorphism may have a great clinical usefulness in a primary prevention setting, since apo(a) phenotypes could be used together with Lp(a) levels as strong genetic predictors of atherothrombosis. The analysis of apo(a) polymorphism appears to be particularly useful in healthy subjects with a family history of atherothrombotic diseases, in patients with diseases at high cardiovascular risk (diabetes, hypertension, hypercholesterolemia) and in subjects with conditions modifying Lp(a) levels.
 ...
PMID:Genetics and cardiovascular risk: a role for apolipoprotein(a) polymorphism. 1037 86

Lipoprotein(a) (Lp(a)) with atherogenic and thrombotic properties has been frequently studied in diabetes, because a high cardiovascular risk has been reported both in type 1 and type 2 diabetes. Few studies have considered genetic factors, especially the isoforms of apolipoprotein(a). The aim of this work is to determine the distribution of apo(a) phenotypes in the serum of 148 diabetic patients (59 type 1, 89 type 2) with or without vascular complications. Apo(a) phenotypes are determined using 4-15% sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by immunoblotting (PhastSystem - Pharmacia). An inverse relationship is observed between Lp(a) serum concentration and the apparent molecular mass of apo(a) isoforms: type 1 r=- 0.61, p<0.01; type 2 r=- 0.55, p<0.01. The frequency of apo(a) isoforms is significantly different between type 1 and type 2 diabetes mellitus. A higher prevalence of isoforms of low molecular weight was observed in the type 2 diabetic population.
Diabetes Metab 2000 Apr
PMID:Determination of lipoprotein(a) concentrations and apolipoprotein(a) molecular weights in diabetic patients. 1080 24


<< Previous 1 2