Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disease caused by at least three different genes. The renal and extrarenal clinical manifestations, and the systemic complications due to cystic and non-cystic abnormalities in ADPKD patients have been widely investigated. Cellular and molecular aspects of cystogenetic mechanisms concern epithelial tubular cell proliferation, remodelling of extracellular matrix, fluid secretion and accumulation, and relations between cell proliferation and apoptosis. In vitro studies on cystogenesis suggest a key role of cell-to-cell or cell-to-matrix interactions. Surface proteins mediating cell-to-cell contact, such as E-cadherin (polycystin?), integrin interactions, growth factors, receptor expression, are involved in the process of differentiation of the cellular condition and of the extracellular matrix. Blocking any one of these complex mechanisms should influence the orientation and polarization of epithelial tubular cells and should mediate the inversion of fluid secretion which ends in renal cystogenesis. ADPKD comprises at least three phenotypically indistinguishable but genetically distinct entities, caused by mutations in three autosomal genes: PKD1 (chromosome 16p13.3) is present in about 85% of patients; PKD2 (chromosome 4q13q23) in 10%; PKD3 (unknown chromosome) in a few families. PCR-based mutation detection methods, automated DNA sequencing, and other "functional" methods are used to screen and analyse ADPKD patients. It is not yet known whether the mutations identified so far in PKD1 and PKD2 inactivate the genes or generate an aberrant product. The products of PKD1 and PKD2 genes have been called polycystin 1 and 2. Polycystins are members of a family of interactive proteins involved in complex adhesive cell-cell, cell-matrix, protein-protein, and protein-carbohydrate interactions in the extracellular compartment, and are involved in the same pathway (ion channel regulator? ion channel? pore?) where mutations in only one of the simple genes (PKD3 too?) may cause the ADPKD phenotype. Genotype-phenotype correlations, in terms of disease severity and/or progression to end-stage renal disease, probably depend on other factors, both genetic and environmental (for instance: DD genotype of the ACE gene in ADPKD hypertensive patients), that might influence the clinical course and progression of ADPKD. The hypothesis of the "two hits" has been proposed to explain at the molecular level the focal nature of cyst formation.
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PMID:Autosomal dominant polycystic kidney disease: clinical and genetic aspects. 944 42

Polycystic kidney disease and Alport's syndrome are the most common causes of inherited renal disease in the UK. An average GP practice is likely to have at least six patients with autosomal dominant polycystic kidney disease (ADPKD). The disorder is characterised by the formation of fluid-filled cysts in the kidneys resulting in progressive renal impairment. Mutations in two genes have been identified. The PKD1 gene abnormality is responsible for 85% of cases of ADPKD, patients with PKD2 mutations typically present later and progress more slowly. Patients with ADPKD can present with a positive family history, hypertension, flank pain, haematuria, renal insufficiency or proteinuria. The diagnosis has traditionally been based on ultrasound imaging. Screening will reduce the incidence of a late diagnosis when renal disease is advanced but a normal ultrasound scan in those under 30 years old is not conclusive. It is not recommended that children are screened. The key to minimising the rate of progressive disease is tight BP control. ACE inhibitors are recommended as the initial antihypertensive agent unless contraindicated. Alport's syndrome is a disorder characterised by abnormal type IV collagen which is found in the kidney, eyes, skin and ears. Around one in ten practices are likely to have a patient with Alport's syndrome. Eighty per cent of patients have the X-linked form of the disease. All first-degree relatives of a patient with confirmed Alport's syndrome should be offered screening. The combination of reduced hearing and urinary abnormalities in a young boy should alert GPs to consider this as a possible diagnosis and initiate referral. Diagnosis can be confirmed by renal or skin biopsy.
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PMID:Improving recognition of inherited renal disease. 2249 4

Autosomal Polycystic Kidney Disease ( ADPKD) is the most common inherited renal disease. ADPKD is caused by mutations in PKD1 and PKD2, encoding polycystin 1 and 2, respectively. ADPKD is a systemic disease, with renal and extrarenal involvement. Renal disease is characterized by formation and growth of cysts, with progressive destruction of renal parenchyma and development of End Stage Renal Disease (ESRD) in about 50% of affected individuals at the age of 60 years. Extrarenal disease usually involves the liver, heart and vasculature. Cardiovascular manifestations occur in a high percentage of patients with ADPKD, including hypertension, left ventricular hypertrophy, cardiac valvular abnormalities, and intracranial aneurysms. An early treatment of hypertension may decreased the risk of cardiovascular complications, the leading cause of morbidity and mortality. The antihypertensive agents of choice should be ACE inhibitors and angiotensin II receptor antagonists. In this review, we will focuses on the cardiovascular problems of patients with ADPKD.
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PMID:[ADPKD and Heart]. 2868 33