title: Correlation between iron status and genetic hemochromatosis (codon C282Y) in a large German population.
abstract: BACKGROUND
  Genetic hemochromatosis leads to iron overload in many tissues and may lead to liver cirrhosis and hepatocellular carcinoma. Early diagnosis and therapy are crucial. Since 80-100% of hemochromatosis patients of European origin are homozygous for a cysteine to tyrosine exchange in the HFE gene at codon 282, genetic screening might be useful. Representative population studies are needed to evaluate the phenotype of people heterozygous and homozygous for the C282Y mutation.
  
  
  OBJECTIVE
  To determine the correlation between parameters of iron metabolism and the hemochromatosis genotype in a large population-based study.
  
  
  METHODS
  A representative population-based survey, the Diabetomobil study, analyzed 5,083 German probands. Serum transferrin saturation and ferritin levels were determined, and the C282Y mutation of the HFE gene was analyzed by restriction fragment length polymorphism-polymerase chain reaction analysis.
  
  
  RESULTS
  Nine of 373 probands with a transferrin saturation > 55% (2.4%) and none of 264 randomly selected probands with a transferrin saturation < or = 55% (0%) were homozygous for the C282Y mutation. Three of the nine homozygous probands had ferritin values less than 250 micrograms/L. The frequency of the heterozygous genotype was 8.8%, and the percentage of heterozygous probands increased with increasing levels of transferrin saturation.
  
  
  CONCLUSIONS
  We propose a population screening strategy with an initial transferrin saturation test, followed by genotyping for the C282Y mutation if the transferrin saturation is above 55%, regardless of the ferritin level. Heterozygous individuals with higher transferrin saturation values may be protected against iron loss but may also be more susceptible for certain liver diseases, depending on the simultaneous prevalence of other diseases.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. christian.wrede@klinik.uni-regensburg.de
authors.forename: Christian E
authors.initials: CE
authors.lastname: Wrede
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hutzler
authors.forename: L Cornelius
authors.initials: LC
authors.lastname: Bollheimer
authors.forename: Roland
authors.initials: R
authors.lastname: Buettner
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schöelmerich
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Palitzsch
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005293:Ferritins / Q000097:blood; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006432:Hemochromatosis / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D019683:Penetrance; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D011159:Population Surveillance; D015995:Prevalence; D014168:Transferrin / Q000378:metabolism
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron