title: Hereditary hemochromatosis gene (HFE) mutations C282Y, H63D and S65C in patients with idiopathic dilated cardiomyopathy.
abstract: BACKGROUND
  Hereditary hemochromatosis (HH), a common autosomal recessive disease, leads to excessive iron accumulation in some organs, including the heart. It is therefore not surprising that cardiomyopathy is one of the most severe complications of HH. The HFE gene defects have been thought to contribute to idiopathic dilated cardiomyopathy (IDCM) in some patients, even though the results of genotype analyses have so far been contradictory. Hence we set out here to evaluate the prevalence and potential role of HFE mutations in patients with IDCM.
  
  
  METHODS
  A total of 91 IDCM patients and 102 controls were subjected to HFE mutation analyses, in which C282Y, H63D and S65C mutations were determined for each patient. We also analyzed the impact of the C282Y and H63D mutations on the left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional classes.
  
  
  RESULTS
  The prevalences of heterozygosity for the C282Y, H63D and S65C mutations in the IDCM patients were 13.2%, 22.0% and 2.2%, respectively. LVEDD was significantly higher (P=0.037) in those with the C282Y mutation at the end of the follow-up period than in those with no mutation.
  
  
  CONCLUSIONS
  Our data showed no significant deviations in C282Y, H63D and S65C mutation frequencies between the IDCM patients and controls, suggesting that these mutations do not increase the risk of IDCM. Heterozygosity for the C282Y mutation may nevertheless be a modifying factor contributing to LV dilatation and remodeling.
authors.affiliation: Department of Clinical Chemistry, University of Oulu, P.O. Box 5000, Oulu, Finland. jokkeha@paju.oulu.fi
authors.forename: Jokke
authors.initials: J
authors.lastname: Hannuksela
authors.forename: Mari
authors.initials: M
authors.lastname: Leppilampi
authors.forename: Keijo
authors.initials: K
authors.lastname: Peuhkurinen
authors.forename: Satu
authors.initials: S
authors.lastname: Kärkkäinen
authors.forename: Eija
authors.initials: E
authors.lastname: Saastamoinen
authors.forename: Tiina
authors.initials: T
authors.lastname: Heliö
authors.forename: Maija
authors.initials: M
authors.lastname: Kaartinen
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: Pentti
authors.initials: P
authors.lastname: Nieminen
authors.forename: Seppo
authors.initials: S
authors.lastname: Parkkila
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005838:Genotype; D006432:Hemochromatosis / Q000150:complications / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012720:Severity of Illness Index; D013318:Stroke Volume
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins