title: Polymorphisms in the 5' flanking region of the HFE gene: linkage disequilibrium and relationship to iron homeostasis.
abstract: We have discovered two single-nucleotide polymorphisms in the 5' flanking region of the HFE gene. These mutations are -970 T-->G and -467 C-->G, numbering from the ATG start codon. When a T was present at -970, a C was always found at -467. The C allele was the less common at nt -467 with a gene frequency of 0.31 in white subjects with wild-type HFE. Slightly lower gene frequencies were observed in a small number of Hispanic and African-American subjects and a slightly higher frequency in a few Asian subjects. The less common -467 mutation was found in almost 12 chromosomes that bore the 845G-->A (C282Y) mutation and was significantly more prevalent in chromosomes containing the 187C-->G (H63D) mutation. Although this mutation is near an HNF3B/HFH2 site, its presence did not seem to affect iron metabolism as judged by the serum ferritin or transferrin saturation levels. The tighter association of the -467 polymorphism with the C282Y mutation is consistent with other data that suggest that the C282Y mutation has occurred relatively recently and that the H63D mutation is considerably older.
authors.affiliation: Department of Molecular and Experimental Medicine, Division of Hematology, The Scripps Research Institute, La Jolla, California 92037, USA. beutler@scripps.edu
authors.forename: Ernest
authors.initials: E
authors.lastname: Beutler
authors.forename: Carol
authors.initials: C
authors.lastname: West
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D019143:Evolution, Molecular; D005293:Ferritins / Q000097:blood; D005787:Gene Frequency; D005820:Genetic Testing; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D019189:Iron Metabolism Disorders / Q000453:epidemiology / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D014168:Transferrin / Q000378:metabolism
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins