title: Clinical implications of nonsarcomeric gene polymorphisms in hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is characterized by cardiomyocyte hypertrophy and fibrosis. Although is an autosomal dominant trait, a group of nonsarcomeric genes have been postulated as modifiers of the phenotypic heterogeneity.
  
  
  METHODS
  We prospectively recruited 168 HCM patients and 136 healthy controls from three referral centres. Patients and controls were clinically stable at entry in the study. Nine polymorphisms previously associated with ventricular remodelling were determined: I/D ACE, AGTR1(A1666C), CYP11B2(C344T), PGC1-α(G482S), COLIA1(G2046T), ADRB1(R389G), NOS3(G894T), RETN(-420C>G) and CALM3(-34T>A). Their potential influence on prognosis, assessed by hospital admissions, and their cause were recorded.
  
  
  RESULTS
  The median follow-up time was 49·5 months. Allele and genotype frequencies did not differ between patients and controls. Thirty-six patients (21·5%) required urgent hospitalization (18·5% for heart failure, 22·2% for atrial arrhythmias, 11·1% for ventricular arrhythmias, 29·6% for ischaemic heart disease, 14·8% for stroke and 3·7% for other reasons) with a hospitalization rate of 8·75% per year. Multivariate analysis showed an independent predictive value for noncarriers of polymorphic COL1A1 allele [HR: 2·76(1·26-6·05), P = 0·011] and a trend in homozygous carriers of ADRB1 Arg389 variant [HR: 1·98(0·99-4·02); P = 0·057].
  
  
  CONCLUSIONS
  Our study suggests that COL1A1 polymorphism (2046G>T) is an independent predictor of prognosis in HCM patients supporting the importance of nonsarcomeric genes on clinical prognosis in HCM.
authors.affiliation: Department of Cardiology, Hospital General Universitario de Elche, Alicante, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: García-Honrubia
authors.affiliation: Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Hernández-Romero
authors.affiliation: Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Orenes-Piñero
authors.affiliation: Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Romero-Aniorte
authors.affiliation: Department of Cardiology, Hospital General Universitario, de Alicante, Alicante, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Climent
authors.affiliation: Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: García
authors.affiliation: Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Garrigos-Gómez
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Alcalá, Madrid, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Moro
authors.affiliation: Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Valdés
authors.affiliation: Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Marín
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000235:genetics*; D002147:Calmodulin / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; 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; D020022:Genetic Predisposition to Disease; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017202:Myocardial Ischemia / Q000150:complications / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D052243:Resistin / Q000235:genetics; D020521:Stroke / Q000150:complications / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: C547787:ADRB1 protein, human; C544065:AGTR1 protein, human; D002147:Calmodulin; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C499624:RETN protein, human; D044140:Receptor, Angiotensin, Type 1; D018342:Receptors, Adrenergic, beta-1; D052243:Resistin; D014157:Transcription Factors; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019405:Cytochrome P-450 CYP11B2; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: Hypertrophic cardiomyopathy; nonsarcomeric genes; polymorphisms; prognosis