title: Blood glutathione decrease in subjects carrying lamin A/C gene mutations is an early marker of cardiac involvement.
abstract: Dominant inherited Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B are due to mutations in the LMNA gene encoding lamin A/C and present similar life-threatening cardiac disease, the early diagnosis of which lacks reliable biomarkers. Glutathione depletion characterizes subjects with cardiac diseases of non-genetic aetiology. We examined blood glutathione in 22 LMNA-mutated subjects without altered left ventricular ejection fraction (LVEF>40%) measured by conventional echocardiography. Left and right ventricular (LV/RV) contractility was evaluated using echocardiography implemented with tissue-Doppler echography. Blood glutathione was positively correlated with LV and RV contractility (p<0.05), and was decreased by 23% in subjects with reduced LV/RV contractility compared to subjects with normal contractility. ROC analysis showed that blood glutathione reliably detected reduced LV/RV contractility (AUC-95% CI: 0.90 [0.76-1.04]; p=0.01). Blood glutathione decrease may allow the detection of reduced contractility in muscular dystrophic LMNA-mutated patients with still preserved LVEF.
authors.affiliation: Université Paris Descartes, AP-HP, Département de Cardiologie, Groupe Hospitalier Cochin, F-75014, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Meune
authors.forename: Lara
authors.initials: L
authors.lastname: Khouzami
authors.forename: Karim
authors.initials: K
authors.lastname: Wahbi
authors.forename: Philippe
authors.initials: P
authors.lastname: Caramelle
authors.forename: Valérie
authors.initials: V
authors.lastname: Decostre
authors.forename: Gisèle
authors.initials: G
authors.lastname: Bonne
authors.forename: Françoise
authors.initials: F
authors.lastname: Pecker
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D018592:Cross-Over Studies; D004452:Echocardiography; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005192:Family Health; D005260:Female; D005978:Glutathione / Q000097:blood*; D006331:Heart Diseases / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D012372:ROC Curve; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D013318:Stroke Volume / Q000502:physiology; D055815:Young Adult
chemical_list: D034904:Lamin Type A; D047888:Receptors, Tumor Necrosis Factor, Type I; D005978:Glutathione