title: Involvement of the -420C>G RETN polymorphism in myocardial fibrosis in patients with hypertrophic cardiomyopathy.
abstract: OBJECTIVE
  Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and fibrosis. HCM is an autosomal-dominant disease caused by more than 400 mutations in sarcomeric genes. Changes in nonsarcomeric genes contribute to its phenotypic heterogeneity. Cardiac fibrosis can be studied using late gadolinium enhancement (LGE) cardiac magnetic resonance imaging. We evaluated the potential role of two polymorphisms in nonsarcomeric genes on interstitial fibrosis in HCM.
  
  
  METHODS
  Two polymorphisms in nonsarcomeric genes [ACE (deletion of 287 bp in the 16th intron) and RETN (-420C>G)] were analysed in 146 HCM patients. Cardiac fibrosis was assessed using LGE to determine the number of affected segments.
  
  
  RESULTS
  Allelic frequencies in ACE and RETN polymorphisms were consistent with the Hardy-Weinberg equilibrium (both P > 0.05). We found that the presence of the polymorphic allele in the -420C>G RETN polymorphism was independently associated with the number of affected segments of LGE (P = 0.038). Increased circulating resistin concentration, measured by enzyme-linked immunosorbent assay, was associated with a higher degree of cardiac fibrosis. Myocardial fibrosis, assessed by Masson's trichrome staining, was associated with the -420C>G RETN polymorphism in 46 tissue samples obtained by septal myectomy (P = 0.044).
  
  
  CONCLUSIONS
  The -420C>G RETN polymorphism was independently associated with the degree of cardiac fibrosis, assessed by LGE, in patients with HCM. In addition, there was an association between the polymorphism and the circulating resistin levels as well as with myocardial fibrosis in tissues obtained by myectomy. Investigating the physiological implication of the RETN polymorphism in HCM in combination with the use of imaging technologies might help to establish the severity of disease in patients with HCM.
authors.affiliation: Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain.|Instituto Murciano de Investigaciones Biosanitarias Virgen de la Arrixaca (IMIB), Murcia, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Hernández-Romero
authors.affiliation: Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain.|Instituto Murciano de Investigaciones Biosanitarias Virgen de la Arrixaca (IMIB), Murcia, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Orenes-Piñero
authors.affiliation: Hospital General Universitario de Elche, Alicante, Spain.
authors.forename: A
authors.initials: A
authors.lastname: García-Honrubia
authors.affiliation: Hospital General Universitario, Alicante, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Climent
authors.affiliation: Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain.|Instituto Murciano de Investigaciones Biosanitarias Virgen de la Arrixaca (IMIB), Murcia, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Romero-Aniorte
authors.affiliation: Instituto Murciano de Investigaciones Biosanitarias Virgen de la Arrixaca (IMIB), Murcia, Spain.|CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: C M
authors.initials: CM
authors.lastname: Martínez
authors.affiliation: Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Spain.
authors.forename: M
authors.initials: M
authors.lastname: García-Bautista
authors.affiliation: Hospital General Universitario, Alicante, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martínez
authors.affiliation: Hospital General Universitario, Alicante, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Feliu
authors.affiliation: Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain.|Instituto Murciano de Investigaciones Biosanitarias Virgen de la Arrixaca (IMIB), Murcia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: González
authors.affiliation: Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Cánovas
authors.affiliation: Hospital Universitario La Fe, Valencia, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Montero-Argudo
authors.affiliation: Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain.|Instituto Murciano de Investigaciones Biosanitarias Virgen de la Arrixaca (IMIB), Murcia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Valdés
authors.affiliation: Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain.|Instituto Murciano de Investigaciones Biosanitarias Virgen de la Arrixaca (IMIB), Murcia, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Marín
mesh_terms: D000328:Adult; D000368:Aged; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D005682:Gadolinium; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011868:Radioisotopes; D052243:Resistin / Q000097:blood / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: C499624:RETN protein, human; D011868:Radioisotopes; D052243:Resistin; D005682:Gadolinium; D007703:Peptidyl-Dipeptidase A
keywords: angiotensin-converting enzyme; fibrosis; hypertrophic cardiomyopathy; late gadolinium enhancement; resistin