title: HFE S65C variant is not associated with increased transferrin saturation in voluntary blood donors.
abstract: Two amino acid variants in the HFE gene, C282Y and H63D, have been reported in most cases of hereditary hemochromatosis. A recently discovered novel amino acid variant of HFE, namely S65C, has been implicated to be responsible for a mild form of iron overload. We determined genotypes of the HFE S65C variant in 230 voluntary blood donors with a transferrin saturation >45%, who did not carry the HFE C282Y variant. The control group consisted of 248 first time blood donors who had a transferrin saturation < 45%. We also determined genotypes of the HFE H63D variant in the two groups. For the HFE S65C variant, the frequency of the HFE C65 allele was 1. 7% and 2.2% in the high and low transferrin saturation groups, respectively (p = 0.65). In contrast, for the HFE H63D variant, the frequency of the HFE D63 allele was 24.8% and 14.7% in the high and low transferrin saturation groups, respectively (p = 0.0009). This study demonstrates no association of the HFE C65 allele with the phenotype of high transferrin saturation. The results do not support the use of DNA genotyping for the HFE S65C mutation in population screening studies for hemochromatosis.
authors.affiliation: Department of Medicine, University of Western Ontario, London, Ontario, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Arya
authors.forename: S
authors.initials: S
authors.lastname: Chakrabrati
authors.forename: R A
authors.initials: RA
authors.lastname: Hegele
authors.forename: P C
authors.initials: PC
authors.lastname: Adams
mesh_terms: D000328:Adult; D000483:Alleles; D001782:Blood Donors; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006680:HLA Antigens / Q000097:blood / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000235:genetics*; D006801:Humans; D019190:Iron Overload / Q000097:blood / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008403:Mass Screening; D008565:Membrane Proteins; D014168:Transferrin / Q000235:genetics / Q000378:metabolism*
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin