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).
Bibliographical noteFunding Information:
The HEIRS Study was initiated and funded by the National Heart, Lung, and Blood Institute, in conjunction with the National Human Genome Research Institute. The study is supported by contracts N01-HC05185 (University of Minnesota); N01-HC05186, N01-CM-07003-74, and Minority CCOP (Howard University); N01-HC05188 (University of Alabama at Birmingham); N01-C05189 (Kaiser Permanente Center for Health Research); N01-HC05190 (University of California, Irvine); N01-HC05191 (London Health Sciences Centre); and N01-C05192 (Wake Forest University). Additional support was provided by the University of Alabama at Birmingham General Clinical Research Center (GCRC) grant M01-RR00032, Howard University GCRC grant M01-RR10284, and the University of California, Irvine UCSD/UCI Satellite GCRC grant M01-RR00827, sponsored by the National Center for Research Resources, National Institutes of Health; Howard University Research Scientist Award UH1-HL03679-05 from the National Heart, Lung and Blood Institute and the Office of Research on Minority Health (VRG); and Southern Iron Disorders Center (JCB, RTA).