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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2005-8-2
pubmed:abstractText
It is highly controversial to define the role of angiotensin-converting enzyme (ACE) polymorphisms in essential hypertension. We studied a group of patients in whom hypertension was the major side effect of treatment by cyclosporine A (CsA). This study group comprised 227 Italian patients with nephrotic syndrome, 103 of which were treated with CsA and had different outcome. Forty-nine patients developed serious hypertension that was reversed after withdrawal of drug. ACE haplotypes were determined by a combination of molecular and statistical methods after verifying genotypes of six intragenic single nucleotide polymorphisms in 304 Italian blood donors and assembling them in clades (A, B, C) that include 95% of observed haplotypes. The association between ACE clade combinations and serum enzymatic levels confirmed the previous results about a role of an unidentified genetic variant at the 5' of the intragenic recombination site located near intron 7. ACE clades were then determined in patients, and regression methods were used to analyze variables associated with CsA responsivity and progression to renal failure. ACE genotype and responsiveness to CsA were strictly associated, because homozygosis for ACE B clade was able to influence CsA sensitivity. This highlights the role of 5' variants, which differentiate clades B and C. Other genetic markers were tested to search for possible additive effects. We found that PAI-1 4G allele was associated with progression to renal failure in the group of CsA-treated patients. Our results are in agreement with the hypothesis, raised after experimental results obtained in mouse models, that the effect of ACE polymorphisms on blood pressure is detectable once environmental factors, like CsA treatment in our case, overcome physiological homeostatic mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2357-67
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16002416-Adolescent, pubmed-meshheading:16002416-Adult, pubmed-meshheading:16002416-Blood Pressure, pubmed-meshheading:16002416-Case-Control Studies, pubmed-meshheading:16002416-Child, pubmed-meshheading:16002416-Child, Preschool, pubmed-meshheading:16002416-Cyclosporine, pubmed-meshheading:16002416-Enzyme Inhibitors, pubmed-meshheading:16002416-Female, pubmed-meshheading:16002416-Genotype, pubmed-meshheading:16002416-Haplotypes, pubmed-meshheading:16002416-Humans, pubmed-meshheading:16002416-Hypertension, pubmed-meshheading:16002416-Infant, pubmed-meshheading:16002416-Male, pubmed-meshheading:16002416-Peptidyl-Dipeptidase A, pubmed-meshheading:16002416-Phenotype, pubmed-meshheading:16002416-Plasminogen Activator Inhibitor 1, pubmed-meshheading:16002416-Polymorphism, Genetic, pubmed-meshheading:16002416-Quantitative Trait Loci, pubmed-meshheading:16002416-Renal Insufficiency, pubmed-meshheading:16002416-Retrospective Studies, pubmed-meshheading:16002416-Treatment Outcome
pubmed:year
2005
pubmed:articleTitle
Angiotensin-converting enzyme (ACE) haplotypes and cyclosporine A (CsA) response: a model of the complex relationship between ACE quantitative trait locus and pathological phenotypes.
pubmed:affiliation
Department of Nephrology, G. Gaslini Institute, Genova, Italy. pcatarsi@libero.it
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't