Heme carrier protein 1 (HCP1) genetic variants in the Hemochromatosis and Iron Overload Screening (HEIRS) Study participants.
Heme carrier protein 1 (HCP1) has been identified as a possible heme carrier by in vitro analysis. To determine the association of mutations within the HCP1 gene with iron phenotypes, we examined the entire coding region of the HCP1 gene in 788 US and Canadian participants selected from the Hemochromatosis and Iron Overload Screening (HEIRS) Study using denaturing high-performance liquid chromatography. We sequenced the exon and flanking intronic regions if variants were detected. We tested 298 non-C282Y homozygotes from four racial/ethnic backgrounds (White, Black, Asian, and Hispanic) selected because they had high serum ferritin (SF) and transferrin saturations (TS). As controls, we chose 300 other random participants of the same racial/ethnic backgrounds from the same geographic locations. From the 333 HEIRS Study C282Y homozygotes, we selected 75 based on high SF and TS, 75 based on low SF and TS; and 75 were selected randomly as controls. Thirty-five of the randomly selected C282Y homozygotes were also included in the high and the low SF and TS groups due to numerical limitations. We identified eight different HCP1 genetic variants; each occurred in a heterozygous state. Except one, each was found in a single HEIRS Study participant. Thus, HCP1 variants are infrequent in the populations that we tested. Five HEIRS Study participants had non-synonymous, coding region HCP1 variants. Each of these five had TS above the 84th gender- and ethnic/racial group-specific percentile (TS percentiles: 84.7, 91.3, 97.9, 99.5, and 99.9).
Wang
XinJing
X
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. wangx6@mail.nih.gov
Leiendecker-Foster
Catherine
C
Acton
Ronald T
RT
Barton
James C
JC
McLaren
Christine E
CE
McLaren
Gordon D
GD
Gordeuk
Victor R
VR
Eckfeldt
John H
JH
D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D005091:Exons / Q000235:genetics; D006432:Hemochromatosis / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D020125:Mutation, Missense; D009691:Nucleic Acid Denaturation; D017354:Point Mutation; D058979:Proton-Coupled Folate Transporter; D044469:Racial Groups / Q000235:genetics; D012494:Sampling Studies; D014168:Transferrin / Q000032:analysis; D014481:United States / Q000453:epidemiology
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D058979:Proton-Coupled Folate Transporter; C505058:SLC46A1 protein, human; D014168:Transferrin; D007501:Iron