title: Prognostic value of two polymorphisms in non-sarcomeric genes for the development of atrial fibrillation in patients with hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Several non-sarcomeric genes have been postulated to act as modifiers in the phenotypic manifestations of hypertrophic cardiomyopathy (HCM). The development of atrial fibrillation (AF) in HCM has adverse prognostic implications with increased thromboembolism and functional class impairment.
  
  
  OBJECTIVE
  We tested the hypothesis that 2 non-sarcomeric genes [CYP11B2 (-344T>C) and COL1A1 (2046G>T)] are associated with the development of AF.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Two polymorphisms in non-sarcomeric genes [CYP11B2 (-344T>C) and COL1A1 (2046G>T)] were analysed in 159 HCM patients (49.3 ± 14.9 years, 70.6% male) and 136 controls. All subjects were clinically stable and in sinus rhythm at entry in the study, without ischemic heart disease or other significant co-morbidities that could mask the effect of the analysed polymorphisms (i.e. previous AF). Thirty-nine patients (24.4%) developed AF during a median follow-up of 49.5 months.
  
  
  RESULTS
  Patients with the -344T>C polymorphism in CYP11B2 gene had a higher risk for AF development [HR: 3.31 (95% CI 1.29-8.50); P = 0.008]. In a multivariate analysis, the presence of the C allele in CYP11B2 gene [HR: 3.02 (1.01-8.99); P = 0.047], previous AF [HR: 2.81 (1.09-7.23); P = 0.033] and a left atrial diameter of ≥42 mm [HR: 2.69 (1.01-7.18); P = 0.048] were independent predictors of AF development. The presence of the polymorphic allele was associated with higher aldosterone serum levels.
  
  
  CONCLUSIONS
  We have shown for the first time that the CYP11B2 polymorphism is an independent predictor for AF development in HCM patients. This highlights the importance of non-sarcomeric genes in the phenotypic heterogeneity of HCM. The association with higher aldosterone serum levels could relate to greater fibrosis and cardiac remodelling.
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: E
authors.initials: E
authors.lastname: Orenes-Piñero
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: D
authors.initials: D
authors.lastname: Hernández-Romero
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: A I
authors.initials: AI
authors.lastname: Romero-Aniorte
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: M
authors.initials: M
authors.lastname: Martínez
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: A
authors.initials: A
authors.lastname: García-Honrubia
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: L
authors.initials: L
authors.lastname: Caballero
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: N
authors.initials: N
authors.lastname: Garrigos-Gómez
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Andreu-Cayuelas
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: J
authors.initials: J
authors.lastname: González
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: E
authors.initials: E
authors.lastname: Feliu
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: V
authors.initials: V
authors.lastname: Climent
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: F
authors.initials: F
authors.lastname: Nicolás-Ruiz
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: G
authors.initials: G
authors.lastname: De La Morena
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: M
authors.initials: M
authors.lastname: Valdés
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
authors.forename: G Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK fcomarino@hotmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Marín
mesh_terms: D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D001281:Atrial Fibrillation / Q000097:blood / Q000209:etiology / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2