title: HFE mutations in Caucasian participants of the Hemochromatosis and Iron Overload Screening study with serum ferritin level <1000 µg/L.
abstract: BACKGROUND
  Many patients referred for an elevated serum ferritin level <1000 µg⁄L are advised that they likely have iron overload and hemochromatosis.
  
  
  OBJECTIVE
  To determine the prevalence of HFE mutations in the hemochromatosis gene for 11 serum ferritin concentration intervals from 200 µg⁄L to 1000 µg⁄L in Caucasian participants in a primary care, population-based study.
  
  
  METHODS
  The Hemochromatosis and Iron Overload Screening study screened 99,711 participants for serum ferritin levels, transferrin saturation and genetic testing for the C282Y and H63D mutations of the HFE gene. This analysis was confined to 17,160 male and 27,465 female Caucasian participants because the HFE C282Y mutation is rare in other races. Post-test likelihood was calculated for prediction of C282Y homozygosity from a ferritin interval. A subgroup analysis was performed in participants with both an elevated serum ferritin level and transferrin saturation.
  
  
  RESULTS
  There were 3359 male and 2416 female participants with an elevated serum ferritin level (200 µg⁄L to 1000 µg⁄L for women, 300 µg⁄L to 1000 µg⁄L for men). There were 69 male (2.1%) and 87 female (3.6%) C282Y homozygotes, and the probability of being a homozygote increased as the ferritin level increased. Post-test likelihood values were 0.3% to 16% in men and 0.3% to 30.4% in women.
  
  
  CONCLUSIONS
  Iron loading HFE mutations are unlikely to be the most common cause of an elevated serum ferritin level in patients with mild hyperferritinemia. Patients should be advised that there are many causes of an elevated serum ferritin level including iron overload.
authors.affiliation: London Health Services Centre, London, Ontario, Canada. padams@uwo.ca
authors.forename: Paul C
authors.initials: PC
authors.lastname: Adams
authors.forename: Christine E
authors.initials: CE
authors.lastname: McLaren
authors.forename: Mark
authors.initials: M
authors.lastname: Speechley
authors.forename: Gordon D
authors.initials: GD
authors.lastname: McLaren
authors.forename: James C
authors.initials: JC
authors.lastname: Barton
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
mesh_terms: D000328:Adult; D005260:Female; D005293:Ferritins / Q000097:blood*; D005820:Genetic Testing; D006432:Hemochromatosis / Q000175:diagnosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000175:diagnosis / Q000235:genetics*; D016013:Likelihood Functions; D008297:Male; D008403:Mass Screening / Q000379:methods; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D015995:Prevalence; D012737:Sex Factors; D014168:Transferrin / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins