title: Impact of HLA-H mutations on iron stores in healthy elderly men and women.
abstract: The DNA of 287 healthy white elderly volunteers in the New Mexico Aging Process Study, between 63 and 91 years of age, was examined for mutations of the HLA-H gene at nt 845 and nt 187. None were found to be homozygous for the 845A mutation and there were no gender differences in the percentage of the various mutations. The frequency of the 845A mutation was 0.061 resulting in a carrier frequency of 12.2%. The frequency of the 187G mutation was 0.136 resulting in a carrier frequency of 19.9% for a single mutation; 2.4% were compound heterozygous, 834A/187G and 2.4% were homozygous for the 187G mutation. After excluding 5 men and 4 women with microcytic or macrocytic anemia, mean percent transferrin saturation (PSAT) and iron stores, as estimated from serum ferritin concentrations, were calculated for each mutation. Estimated iron stores were normally distributed (range approximately 50 to 1,550 mg) with men (n=111) having significantly higher mean estimated iron stores than women (n=167), 826 +/- 318 and 753 +/- 287 mg, respectively. More men, 15 of 28, (54%) with estimated iron stores in the upper quartile, >/= 1,050 mg, had a HLA-H mutation compared to 25 of 83 (30%) who had a mutation and whose estimated iron stores were < ,050 mg, P<0.05. Seven were heterozygous for the 845A mutation with mean estimated iron stores of 1,300 +/- 127 mg, 7 were heterozygous for the 187G mutation with mean estimated iron stores of 1,439 mg. Similar differences were not noted in women. Even though the potential role of the 187G mutation in the phenotypic expression of HH is less certain than the 845A mutation, the increase in PSAT seen in men with the 187G mutation and the equal distribution of 845A and 187G mutations seen with iron stores >/= 1,050 mg lends support for the involvement of the 187G mutation, or a linked mutation, in iron metabolism. We concluded that men having either a single chromosomal 845A and/or 187G mutation results in higher PSAT's and estimated iron stores than if no HLA-H mutation were present.
authors.affiliation: Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. pgarry@salud.unm.edu
authors.forename: P J
authors.initials: PJ
authors.lastname: Garry
authors.forename: G D
authors.initials: GD
authors.lastname: Montoya
authors.forename: R N
authors.initials: RN
authors.lastname: Baumgartner
authors.forename: H C
authors.initials: HC
authors.lastname: Liang
authors.forename: T M
authors.initials: TM
authors.lastname: Williams
authors.forename: S G
authors.initials: SG
authors.lastname: Brodie
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000235:genetics; D000748:Anemia, Macrocytic / Q000097:blood / Q000235:genetics; D004032:Diet; D005260:Female; D005293:Ferritins / Q000097:blood; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012016:Reference Values; D012727:Sex Characteristics; D014168:Transferrin / Q000378:metabolism
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron