title: HFE C282Y homozygotes aged 25-29 years at HEIRS Study initial screening.
abstract: We characterized HFE C282Y homozygotes aged 25-29 years in the HEmochromatosis and IRon Overload Screening (HEIRS) Study using health questionnaire responses, transferrin saturation (TfSat), serum ferritin (SF), and HFE genotyping. In eight homozygotes, we used denaturing high-performance liquid chromatography and sequencing to search for HFE2 (= HJV), TFR2, HAMP, SLC40A1 (= FPN1), and FTL mutations. Sixteen of 4,008 White or Hispanic participants aged 25-29 years had C282Y homozygosity (15 White, 1 Hispanic); 15 were previously undiagnosed. Eleven had elevated TfSat; nine had elevated SF. None reported iron overload-associated abnormalities. No deleterious non-HFE mutations were detected. The prevalence of C282Y homozygosity in White or Hispanic HEIRS Study participants aged 25-29 years did not differ significantly from the prevalence of C282Y homozygosity in older White or Hispanic HEIRS Study participants. The prevalences of reports of iron overload-associated abnormalities were not significantly different in these 16 C282Y homozygotes and in HFE wt/wt control participants aged 25-29 years who did not report having hemochromatosis or iron overload. We conclude that C282Y homozygotes aged 25-29 years diagnosed by screening infrequently report having iron overload-associated abnormalities, although some have elevated SF. Screening using an elevated TfSat criterion would fail to detect some C282Y homozygotes aged 25-29 years.
authors.affiliation: Southern Iron Disorders Center, Birmingham, Alabama, USA. ironmd@dnamail.com
authors.forename: James C
authors.initials: JC
authors.lastname: Barton
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Acton
authors.forename: Catherine
authors.initials: C
authors.lastname: Leiendecker-Foster
authors.forename: Laura
authors.initials: L
authors.lastname: Lovato
authors.forename: Paul C
authors.initials: PC
authors.lastname: Adams
authors.forename: Gordon D
authors.initials: GD
authors.lastname: McLaren
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
authors.forename: Christine E
authors.initials: CE
authors.lastname: McLaren
authors.forename: David M
authors.initials: DM
authors.lastname: Reboussin
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
authors.forename: Mark R
authors.initials: MR
authors.lastname: Speechley
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Reiss
authors.forename: Richard D
authors.initials: RD
authors.lastname: Press
authors.forename: Fitzroy W
authors.initials: FW
authors.lastname: Dawkins
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000235:genetics; D001052:Apoferritins; D027682:Cation Transport Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005293:Ferritins / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D011990:Receptors, Transferrin / Q000235:genetics; D000098742:Ferroportin
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C507433:FTL protein, human; C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D000098742:Ferroportin; D005293:Ferritins; D001052:Apoferritins