Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of present study was to determine if factor V Leiden (FVL) mutation and angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism are associated with diabetic nephropathy (DN) among Kurdish population from Western Iran. This case-control study comprised 144 unrelated adult type 2 diabetic mellitus patients (T2DM) including 72 patients with microalbuminuria and 72 age and sex matched patients without nephropathy. The ACE I/D polymorphism and FVL mutation were detected by polymerase chain reaction (PCR) and PCR-RFLP, respectively. The frequency of FVL G1691A and ACE D allele in T2DM patients with microalbuminuria were 1.6 and 57%, respectively and in normoalbuminuric T2DM patients were 4.9 and 58.3%, respectively (P > 0.05). ACE genotypes affected on serum ACE activity and a better response to ACE inhibitor therapy (captopril) compared to angiotensin II receptor antagonist (losartan) was obtained with significant reduction of ACE activity in diabetic patients without nephropathy carrying DD genotype. However, the beneficial effect of losartan therapy was observed in microalbuminuric patients with II genotype compared to ID and DD genotypes.
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PMID:The frequency of factor V Leiden mutation, ACE gene polymorphism, serum ACE activity and response to ACE inhibitor and angiotensin II receptor antagonist drugs in Iranians type II diabetic patients with microalbuminuria. 2085 44

Whereas it is generally perceived to be harmful, enhanced coagulation activation can also convey salutary effects. The high prevalence of the prothrombotic factor V Leiden (FVL) mutation in whites has been attributed to a positive selection pressure (eg, resulting from reduced blood loss or improved survival in sepsis). The consequences of enhanced coagulation activation, as observed in FVL carriers, on microvascular diabetic complications remain unknown. We therefore investigated the role of FVL in diabetic nephropathy. In heterozygous or homozygous diabetic FVL mice, albuminuria and indices of diabetic nephropathy were reduced compared with diabetic wild-type mice. This was associated with reduced glomerular apoptosis and preservation of podocytes in diabetic FVL-positive mice. In vitro, low-dose thrombin (50pM) prevented, whereas high-dose thrombin (20nM) aggravated, glucose-induced apoptosis in podocytes. In diabetic patients, the FVL mutation, but not the plasminogen activator inhibitor-1 4G/5G polymorphism, is associated with reduced albuminuria, which is consistent with a nephroprotective role of low but sustained thrombin generation. Consistently, anticoagulation of diabetic FVL-positive mice with hirudin abolished the nephroprotective effect. These results identify a nephroprotective function of low but sustained thrombin levels in FVL carriers, supporting a dual, context-dependent function of thrombin in chronic diseases.
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PMID:Low but sustained coagulation activation ameliorates glucose-induced podocyte apoptosis: protective effect of factor V Leiden in diabetic nephropathy. 2156

Management of end-stage renal disease is the mainstay of prevention of renal vascular complications and kidney rejection. We sought to describe the association of some disorders such as diabetic nephropathy, polycystic renal disease, hypertension, and thrombophilia with renal failure and discuss possible mechanisms explaining the implication of the thrombophilic states in kidney allograft thrombosis and renal rejection. Five hundred and sixty-eight patients were included in this case-control study and multivariate analysis was applied. Cases and controls were tested for all major types of thrombophilia. Diabetic nephropathy, autosomal dominant polycystic kidney disease, hypertension, and smoking are the strongest causal agents of end-stage renal disease in Tunisia. It should also be noted that the prevalence of factor V Leiden (P = 0.05) and protein C deficiency (P = 0.005) were significantly higher in ESRD patients awaiting renal transplantation than controls. The present study has raised the possibility that thrombophilic factors may play a pathophysiological role in renal failure. These results will serve as a basis for anticoagulant prophylaxis aimed at preventing kidney rejection and renal allograft thrombosis.
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PMID:Thrombophilic disorders: a real threat to patients with end-stage renal disease on hemodialysis and at the time of renal transplantation. 2252 93

The factor V Leiden (FVL) mutation is the most frequent genetic cause of venous thrombosis in Caucasians. However, protective effects have been suggested to balance the disadvantages. We have recently observed protective effects of FVL mutation on experimental diabetic nephropathy in mice as well as an association with reduced albuminuria in two human cohorts of diabetic patients. In the present study we aimed to reevaluate these findings in an independent, larger cohort of 1905 Caucasians at risk of developing type 2 diabetes and extend possible associations to earlier disease stages of nephropathy. Carriers of FVL mutation had a significantly lower urine albumin excretion (P = 0.03) and tended to have lower plasma creatinine concentrations (P = 0.07). The difference in plasma creatinine concentrations was significant after adjustment for the influencing factors: age, gender, and lean body mass (P = 0.048). These observations at a very early "disease" stage are an important extension of previous findings and suggest that modification of glomerular dysfunction by FVL mutation is relevant during very early stages of diabetic nephropathy. This makes the underlying mechanism an interesting therapeutic target and raises the question whether FVL mutation may also exert protective effects in other glomerulopathies.
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PMID:Lower plasma creatinine and urine albumin in individuals at increased risk of type 2 diabetes with factor v leiden mutation. 2472 85