title: A promoter polymorphism -945C>G in the connective tissue growth factor in heart failure patients with mechanical circulatory support: a new marker for bridge to recovery?
abstract: OBJECTIVE
  Mechanical circulatory support (MCS) creates improvement of cardiac function in a small portion of patients with idiopathic dilated cardiomyopathy (iDCM). Among other factors, cardiomyocyte hypertrophy seems to represent an important prerequisite for MCS-related cardiac recovery. We have previously shown that connective tissue growth factor (CTGF) leads to adaptive cardiomyocyte hypertrophy associated with a protective cardiac function in transgenic mice. To test whether a functional genetic variant in the CTGF promoter impacts MCS-related cardiac recovery, three groups of iDCM patients with and without cardiac recovery on MCS were genotyped.
  
  
  METHODS
  The CTGF promoter variant (c.-945C>G) was analysed in 314 patients with iDCM receiving medical treatment only (Group I). Forty-nine iDCM patients who were either weaned from MCS for more than 6 months (Group II; n=20) or bridged to cardiac transplantation (Group III: n=29) were also genotyped. Patients on MCS were followed up for at least 12 months. Clinical characteristics and outcome on MCS were correlated with the respective genotypes.
  
  
  RESULTS
  The c.-945C>G allele frequencies in 314 iDCM patients (Group I) were similar to controls deposited in the HapMap database or those published in a recent study. There were no differences in allele prevalence between patients with mild to moderate iDCM (Group I) compared with patients with severe iDCM requiring MCS (Groups II and III). Intriguingly, 50% of patients who were weaned from MCS (Group II) were homozygous for the G allele compared with only 17.2% of patients included in Group III, which is a significant difference (P=0.03).
  
  
  CONCLUSIONS
  Homozygosity of the promoter-activating G allele in the CTGF_c.-945C>G variant is overrepresented in patients with cardiac recovery on MCS when compared with iDCM patients without cardiac recovery. Further studies are needed to evaluate c.-945C>G as a genetic predictor for clinical outcome on MCS.
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany Charité Research Organisation GmbH, Berlin, Germany maximilian.posch@charite.de.
authors.forename: Maximilian G
authors.initials: MG
authors.lastname: Posch
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany.
authors.forename: Gunther
authors.initials: G
authors.lastname: Schmidt
authors.affiliation: Cardiovascular Genetics, Experimental and Clinical Research Center (ECRC), a Joint Cooperation of the Charité - Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Steinhoff
authors.affiliation: Cardiovascular Genetics, Experimental and Clinical Research Center (ECRC), a Joint Cooperation of the Charité - Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Perrot
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Drews
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Dandel
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krabatsch
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany.
authors.forename: Evgenij V
authors.initials: EV
authors.lastname: Potapov
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000601:surgery; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006353:Heart-Assist Devices; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C526317:CCN2 protein, human; D005819:Genetic Markers; D055513:Connective Tissue Growth Factor
keywords: Bridge-to-recovery; Connective tissue growth factor; Polymorphism; Ventricular assist device