PMID- 35659379
OWN - NLM
STAT- MEDLINE
DCOM- 20220608
LR  - 20220716
IS  - 1601-5223 (Electronic)
IS  - 0018-0661 (Print)
IS  - 0018-0661 (Linking)
VI  - 159
IP  - 1
DP  - 2022 Jun 6
TI  - HLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred 
      hemochromatosis probands with HFE p.C282Y homozygosity.
PG  - 25
LID - 10.1186/s41065-022-00237-w [doi]
LID - 25
AB  - BACKGROUND: Human leukocyte antigen (HLA)-A*03, hemochromatosis ancestral 
      haplotype marker, was associated with greater iron overload in hemochromatosis 
      cohorts reported before discovery of the HFE gene. We sought to learn whether an 
      A*03-linked locus influences phenotypes in referred HFE p.C282Y homozygotes. 
      METHODS: We tabulated these phenotypes in probands with p.C282Y homozygosity: 
      age, transferrin saturation (TS), serum ferritin (SF), conditions related to iron 
      overload, fibrosis-four variables (FIB-4) index and aspartate 
      aminotransferase-to-platelet ratio index (APRI) predictors of severe hepatic 
      fibrosis, and iron removed to achieve depletion (QFe/age). We analyzed phenotypes 
      of men and women separately across three A*03 subgroups. RESULTS: There were 104 
      men (57.8%) and 76 women (42.2%). Mean age (SD) was 49 +/- 13 y. Mean TS was 
      79 +/- 17%. Median SF (range) was 715 microg/L (28, 6103). Related conditions included: 
      hemochromatosis arthropathy (21.7%); type 2 diabetes (18.9%); hypogonadotropic 
      hypogonadism (5.8% of men); cardiomyopathy (0%); and cirrhosis (10.0%). Median 
      QFe/age was 61 mg/y (0, 714). A*03 homozygosity, heterozygosity, and no A*03 
      occurred in 37 (20.6%), 104 (57.8%), and 39 probands (21.7%), respectively. In 
      men, mean TS and median SF were significantly higher in A*03 homozygotes than 
      heterozygotes but not A*03-negative probands. In men, median APRI was 
      significantly lower in A*03 heterozygotes than homozygotes and A*03-negative 
      probands. No other phenotypes, including QFe/age, differed significantly across 
      A*03 subgroups in either men or women. CONCLUSIONS: Our results suggest that an 
      A*03-linked locus does not influence phenotypes in referred HFE p.C282Y 
      homozygotes. It is unlikely that heritable factors that modify phenotypes of 
      p.C282Y homozygotes are linked to the hemochromatosis ancestral haplotype.
CI  - (c) 2022. The Author(s).
FAU - Barton, James C
AU  - Barton JC
AD  - Southern Iron Disorders Center, Birmingham, AL, USA. bartonjames336@gmail.com.
AD  - Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. 
      bartonjames336@gmail.com.
FAU - Barton, J Clayborn
AU  - Barton JC
AD  - Southern Iron Disorders Center, Birmingham, AL, USA.
FAU - Acton, Ronald T
AU  - Acton RT
AD  - Southern Iron Disorders Center, Birmingham, AL, USA.
AD  - Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 
      USA.
LA  - eng
PT  - Journal Article
DEP - 20220606
PL  - England
TA  - Hereditas
JT  - Hereditas
JID - 0374654
RN  - 0 (HFE protein, human)
RN  - 0 (HLA-A Antigens)
RN  - 0 (Hemochromatosis Protein)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Proteins)
SB  - IM
MH  - *Diabetes Mellitus, Type 2/complications
MH  - Female
MH  - HLA-A Antigens/genetics
MH  - Haplotypes
MH  - *Hemochromatosis/genetics
MH  - Hemochromatosis Protein/genetics
MH  - Histocompatibility Antigens Class I/genetics
MH  - Homozygote
MH  - Humans
MH  - *Iron Overload/complications/genetics
MH  - Membrane Proteins/genetics
MH  - Phenotype
PMC - PMC9169309
OTO - NOTNLM
OT  - APRI
OT  - Ancestral haplotype
OT  - FIB-4
OT  - Haplotype
OT  - Iron overload
COIS- The authors declare that they have no competing interests.
EDAT- 2022/06/07 06:00
MHDA- 2022/06/09 06:00
PMCR- 2022/06/06
CRDT- 2022/06/06 10:47
PHST- 2022/01/20 00:00 [received]
PHST- 2022/05/11 00:00 [accepted]
PHST- 2022/06/06 10:47 [entrez]
PHST- 2022/06/07 06:00 [pubmed]
PHST- 2022/06/09 06:00 [medline]
PHST- 2022/06/06 00:00 [pmc-release]
AID - 10.1186/s41065-022-00237-w [pii]
AID - 237 [pii]
AID - 10.1186/s41065-022-00237-w [doi]
PST - epublish
SO  - Hereditas. 2022 Jun 6;159(1):25. doi: 10.1186/s41065-022-00237-w.