Linked Life Data

17452507

Source:http://linkedlifedata.com/resource/pubmed/id/17452507

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-5-24
pubmed:abstractText
The angiotensin-converting enzyme (ACE) I/D and the alpha-adducin (ADD1) Gly460Trp polymorphisms are associated with cardiovascular risk factors. In a prospective population study and in cell models, we investigated the combined effects of these 2 polymorphisms. We randomly recruited 1287 white subjects (women: 50.0%; mean age: 55.9 years). We obtained outcomes from registries and repeat examinations (median 3). Over 9.0 years (median), 178 fatal or nonfatal cardiovascular events occurred. In ADD1 Trp allele carriers, the multivariate-adjusted hazard ratios associated with ACE DD versus I were 1.72 (P=0.007) for total mortality, 2.35 (P=0.02) for cardiovascular mortality, 2.02 (P=0.005) for all cardiovascular events, and 2.59 (P=0.03) for heart failure. In contrast, these hazard ratios did not reach significance in ADD1 GlyGly homozygotes (0.08<or=P<or=0.90). The positive predictive value and attributable risk associated with ACE DD homozygosity combined with mutated ADD1 were 36.2% and 10.3%, respectively. To clarify our epidemiological observations, we investigated the effects of mutated human ADD1 on the membrane-bound ACE activity in fibroblasts from 51 volunteers and in transfected human embryonic kidney cells (31 experiments). In fibroblasts (5.10 versus 3.63 nanomoles of generated hippuric acid per milligram of protein per minute; P=0.0021) and human embryonic kidney cells (1.086 versus 0.081 nmol/mg per minute; P=0.017), the membrane-bound ACE activity increased in the presence but not absence of the ADD1 Trp allele. In conclusion, the combination of ACE DD homozygosity and mutated ADD1 worsened cardiovascular prognosis to a similar extent as classic risk factors, possibly because of increased membrane-bound ACE activity in subjects carrying the ADD1 Trp allele.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1291-7
pubmed:meshHeading
pubmed-meshheading:17452507-Aged, pubmed-meshheading:17452507-Calmodulin-Binding Proteins, pubmed-meshheading:17452507-Cardiovascular Diseases, pubmed-meshheading:17452507-Cell Line, pubmed-meshheading:17452507-Cells, Cultured, pubmed-meshheading:17452507-Diuretics, pubmed-meshheading:17452507-Female, pubmed-meshheading:17452507-Glycine, pubmed-meshheading:17452507-Homozygote, pubmed-meshheading:17452507-Humans, pubmed-meshheading:17452507-Hypertension, pubmed-meshheading:17452507-Male, pubmed-meshheading:17452507-Middle Aged, pubmed-meshheading:17452507-Mutation, pubmed-meshheading:17452507-Peptidyl-Dipeptidase A, pubmed-meshheading:17452507-Polymorphism, Single Nucleotide, pubmed-meshheading:17452507-Predictive Value of Tests, pubmed-meshheading:17452507-Prognosis, pubmed-meshheading:17452507-Prospective Studies, pubmed-meshheading:17452507-Risk Factors, pubmed-meshheading:17452507-Tryptophan
pubmed:year
2007
pubmed:articleTitle
Angiotensin-converting enzyme I/D and alpha-adducin Gly460Trp polymorphisms: from angiotensin-converting enzyme activity to cardiovascular outcome.
pubmed:affiliation
Studies Coordinating Centre, Division of Hypertension and Cardiovascular Research, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't