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The influence of the angiotensin I converting enzyme genotype in familial hypertrophic cardiomyopathy varies with the disease gene mutation

dc.contributor.authorTesson F.
dc.contributor.authorDufour C.
dc.contributor.authorMoolman J.C.
dc.contributor.authorCarrier L.
dc.contributor.authorAl-Mahdawi S.
dc.contributor.authorChojnowska L.
dc.contributor.authorDubourg O.
dc.contributor.authorSoubrier F.
dc.contributor.authorBrink P.
dc.contributor.authorKomajda M.
dc.contributor.authorGuicheney P.
dc.contributor.authorSchwartz K.
dc.contributor.authorFeingold J.
dc.date.accessioned2011-05-15T15:59:43Z
dc.date.available2011-05-15T15:59:43Z
dc.date.issued1997
dc.identifier.citationJournal of Molecular and Cellular Cardiology
dc.identifier.citation29
dc.identifier.citation2
dc.identifier.issn222828
dc.identifier.other10.1006/jmcc.1996.0332
dc.identifier.urihttp://hdl.handle.net/10019.1/11330
dc.description.abstractFamilial hypertrophic cardiomyopathy is an autosomal dominant genetically heterogeneous disease characterized by a partial penetrance and variable expressivity. Previous studies showed that the extent of hypertrophy is influenced by the angiotensin I converting enzyme insertion/deletion (I/D) polymorphism. Recently, molecular genetic analysis revealed the existence of healthy carriers and that as many as a quarter of genetically affected individuals do not express the disease. This data prompted us to re-investigate the role of the angiotensin I converting enzyme polymorphism on hypertrophy by assessing both clinically affected individuals and healthy carriers. For this, several families with mutations in the cardiac myosin binding protein C or the β-myosin heavy chain genes were analysed. The mean maximal intraventricular septum thickness was compared as a function of angiotensin I converting enzyme genotypes in all genetically affected individuals (n = 114), and in subsets of subjects carrying either a splice acceptor site mutation in the cardiac myosin binding protein C gene (n = 33), or various missense mutations in the cardiac β-myosin heavy chain gene (n = 81) or finally, mutations in the Arg403 codon of the β-myosin heavy chain gene (n = 54). Significant association between the D allele and hypertrophy was observed only in the case of Arg403 codon mutations (mean septum thickness for subjects with the DD genotype: 19.3 ± 2.7 mm; with the ID genotype: 13.4 ± 1.3 mm and with the II genotype: 11.0 ± 0.9 mm; P < 0.02). These results were confirmed by the χ2 test showing an over-representation of DD genotype in patients carrying an Arg403 codon mutation associated with septal hypertrophy (P < 0.05). Our data confirms that the angiotensin I converting enzyme genotypes can influence the phenotypic expression of hypertrophy and shows that this influence depends on the mutation, raising the concept of multiple genetic modifiers in familial hypertrophic cardiomyopathy.
dc.subjectbinding protein
dc.subjectdipeptidyl carboxypeptidase
dc.subjectmyosin heavy chain
dc.subjectadult
dc.subjectaged
dc.subjectarticle
dc.subjectautosomal dominant inheritance
dc.subjectbinding site
dc.subjectcodon
dc.subjectcontrolled study
dc.subjectfemale
dc.subjectgene deletion
dc.subjectgene expression
dc.subjectgene insertion
dc.subjectgene mutation
dc.subjectgenetic analysis
dc.subjectgenotype
dc.subjectheart ventricle septum
dc.subjectheterozygote
dc.subjecthuman
dc.subjecthypertrophic cardiomyopathy
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectmissense mutation
dc.subjectmolecular genetics
dc.subjectphenotype
dc.subjectpriority journal
dc.subjectAdult
dc.subjectCardiomyopathy, Hypertrophic
dc.subjectCarrier Proteins
dc.subjectFemale
dc.subjectHeterozygote
dc.subjectHumans
dc.subjectMale
dc.subjectModels, Genetic
dc.subjectMutation
dc.subjectMyosin Heavy Chains
dc.subjectPedigree
dc.subjectPeptidyl-Dipeptidase A
dc.subjectPolymorphism, Genetic
dc.titleThe influence of the angiotensin I converting enzyme genotype in familial hypertrophic cardiomyopathy varies with the disease gene mutation
dc.typeArticle
dc.description.versionArticle


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