Document Detail


ACE gene insertion/deletion polymorphism modulates capillary permeability in hypertension.
MedLine Citation:
PMID:  16889537     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A D/D (deletion/deletion) polymorphism within the ACE (angiotensin 1-converting enzyme) gene increases the risk of microalbuminuria, a predictor of atherosclerotic vascular disease, in essential hypertension. It is unknown, however, whether this genetic profile is accompanied by disturbed macromolecular permeability of systemic capillary endothelium, possibly in the context of generalized endothelial dysfunction. In the present study, the ACE gene polymorphism was determined by PCR in 79 never-treated uncomplicated hypertensive men and 16 normotensive men as controls. Evaluation variables were TERalb (transcapillary escape rate of albumin; the 1-h decline rate of intravenous (125)I-albumin, a measure of integrity of systemic capillary endothelium), albuminuria and forearm vasodilation to intra-arterial acetylcholine, an index of NO (nitric oxide)-mediated vasomotion, in addition to a series of sensitive parameters of albumin permeation (blood pressure, metabolic status and smoking habits). Analyses were done by comparing D/D homozygotes with grouped I/D (insertion/deletion) and I/I (insertion/insertion) subjects. TERalb was higher in D/D hypertensives, who had higher albuminuria, more frequent microalbuminuria and comparable forearm responsiveness to intra-arterial acetylcholine. Fasting glucose and insulin, insulin sensitivity, 24-h blood pressure, smoking habits and metabolic parameters did not differ between the two groups. TERalb and urine albumin values were positively associated in the hypertensive subjects. In conclusion, ACE D/D homozygosis, independently of several confounding factors, associates with higher TERalb in men with essential hypertension. This may reflect noxious genetic influences on systemic vascular permeability, a critical control mechanism for atherogenesis in the absence of grossly impaired NO-mediated arteriolar responsiveness. The parallel behaviour of TERalb and albuminuria suggests some shared genetically mediated determinant of renal and systemic microvascular abnormalities in hypertension.
Authors:
Giulia Dell'omo; Giuseppe Penno; Laura Pucci; Daniela Lucchesi; Carmen Fotino; Stefano Del Prato; Roberto Pedrinelli
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  111     ISSN:  1470-8736     ISO Abbreviation:  Clin. Sci.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-09     Completed Date:  2007-09-17     Revised Date:  2007-11-01    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  357-64     Citation Subset:  IM    
Affiliation:
Dipartimento Cardio Toracico, Università di Pisa, Pisa, Italy.
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MeSH Terms
Descriptor/Qualifier:
Albuminuria / genetics,  physiopathology
Capillary Permeability / physiology*
Case-Control Studies
DNA Transposable Elements / genetics*
Endothelium, Vascular / physiology
Forearm / blood supply
Gene Deletion*
Genotype
Humans
Hypertension / genetics*,  physiopathology
Middle Aged
Peptidyl-Dipeptidase A / genetics*
Polymorphism, Genetic / genetics*
Vasodilation / genetics
Chemical
Reg. No./Substance:
0/DNA Transposable Elements; EC 3.4.15.1/ACE protein, human; EC 3.4.15.1/Peptidyl-Dipeptidase A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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