title: Low frequency of HFE gene mutations in Croatian patients suspected of having hereditary hemochromatosis.
abstract: BACKGROUND
  Hereditary hemochromatosis (HH) is a common autosomal recessive disorder in populations of European descent. It is characterized by a variable prevalence of mutations in the hemochromatosis gene (HFE) in different countries and a complex relationship between the HFE genotype and the HH phenotype. Genetic analysis has not been conducted in Croatian patients with iron overload. The aim of this study was to determine whether HFE mutations, C282Y, H63D, and S65C were correlated with clinical and biochemical parameters in Croatian patients with suspected HH.
  
  
  METHODS
  Clinical examination, biochemical analysis, and genotyping were performed in 175 patients suspected of having HH. The control group consisted of 350 healthy blood donors.
  
  
  RESULTS
  Among the patients, 20% had genotypes related to HH--7.4% were homozygous for C282Y, 6.3% were compound heterozygous for C282Y and H63D, 5.7% were homozygous for H63D, and 0.6% was compound heterozygous for C282Y and S65C. The allelic frequencies were 14.6% for C282Y mutation, 23.7% for H63D mutation, and 1.4% for S65C mutation. A comparison of the clinical and laboratory profiles of patients revealed that C282Y homozygotes had higher frequencies of all clinical symptoms and higher levels of biochemical parameters than others. The C282Y/H63D compound heterozygotes and H63D homozygotes were found to be clinically important, despite the fact that they were associated with less severe disease.
  
  
  CONCLUSIONS
  Our results show that HFE mutations are responsible for only about 20% of Croatian patients with suspected HH. Screening with biochemical methods and HFE genotyping may be not sufficient for diagnoses in the Croatian population.
authors.affiliation: Department of Gastroenterology, University Hospital Rijeka, Rijeka, Croatia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Milić
authors.forename: Smiljana
authors.initials: S
authors.lastname: Ristić
authors.forename: Nada
authors.initials: N
authors.lastname: Starčević-Čizmarević
authors.forename: Bojana
authors.initials: B
authors.lastname: Brajenović-Milić
authors.forename: Marija
authors.initials: M
authors.lastname: Crnić-Martinović
authors.forename: Miljenko
authors.initials: M
authors.lastname: Kapović
authors.forename: Borut
authors.initials: B
authors.lastname: Peterlin
authors.forename: Davor
authors.initials: D
authors.lastname: Štimac
mesh_terms: D000704:Analysis of Variance; D001774:Blood Chemical Analysis; D017523:Croatia; D005787:Gene Frequency; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D009391:Nephelometry and Turbidimetry; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011795:Surveys and Questionnaires
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins